進階搜尋


   電子論文尚未授權公開,紙本請查館藏目錄
(※如查詢不到或館藏狀況顯示「閉架不公開」,表示該本論文不在書庫,無法取用。)
系統識別號 U0026-2707201020560400
論文名稱(中文) 合併處理放射線與三氧化二砷對於不同p53狀態之人類前列腺癌細胞之抗腫瘤能力的機制探討
論文名稱(英文) Mechanistic study of combination treatment with radiation and arsenic trioxide enhanced anti-tumor effects in human prostate cancer cells with different p53 status
校院名稱 成功大學
系所名稱(中) 環境醫學研究所
系所名稱(英) Institute of Environmental and Occupational Health
學年度 98
學期 2
出版年 99
研究生(中文) 陳怡安
研究生(英文) Yi-An Chen
學號 s7697405
學位類別 碩士
語文別 中文
論文頁數 62頁
口試委員 指導教授-王應然
口試委員-何元順
口試委員-潘敏雄
口試委員-何聖佑
口試委員-陳彥霖
中文關鍵字 前列腺癌  放射線治療  三氧化二砷  自體吞噬  細胞凋亡  p53 
英文關鍵字 Prostate cancer  radiotherapy  arsenic trioxide  autophagy  apoptosis  p53 
學科別分類
中文摘要 前列腺癌(Prostate cancer)為歐美國家常見的男性致死癌症之一,近幾年在亞洲國家前列腺癌的發生率逐漸攀升。放射線治療為常見的前列腺癌治療方式,然而,使用高劑量的放射線會導致陽萎、泌尿道官能障礙、直腸癌等相關副作用。許多研究證實三氧化二砷可提高癌細胞在放射線治療的效果,因而可降低放射線使用劑量。本研究的目的為藉由合併處理三氧化二砷以增加前列腺癌細胞株LNCaP (wild-type p53)與PC-3 (p53 null)對於放射線治療的效果,並探討其相關作用機制。在細胞實驗當中,利用trypan blue計算細胞存活率,並使用流式細胞儀分析細胞週期與藉由annexin V分析早期細胞凋亡,利用acridine orange染色觀察自體吞噬所形成之酸性小泡(AVO),使用穿透式電子顯微鏡觀察PC-3細胞的超顯微結構,並且以西方墨點法分析細胞凋亡與自體吞噬相關蛋白之表現量變化,最後利用nude mice xenograft的實驗模式評估合併處理放射線與三氧化二砷在活體中的影響。結果顯示,前列腺癌細胞株LNCaP與PC-3在合併處理放射線與三氧化二砷後效果皆較單獨處理放射線好。在合併處理的情況下,會增加LNCaP細胞早期細胞凋亡百分比,然而PC-3細胞其細胞凋亡的百分比相較於單獨處理放射線或三氧化二砷並無顯著差異,但會增加PC-3細胞於細胞週期G2/M期的停滯,且於兩株細胞中皆會增加自體吞噬的百分比。此外,相較於單獨處理放射線或三氧化二砷,在LNCaP與PC-3細胞中自體吞噬指標LC3Ⅱ與P62/SQSTM1的表現量均有增加的趨勢,且Akt/mTOR途徑相關蛋白會受到抑制。而在PC-3細胞株中,前處理自體吞噬抑制劑3-MA可降低合併處理誘發的自體吞噬百分比,並提高細胞存活率;前處理PI3K/Akt抑制劑LY294002,則更增加合併處理誘發的自體吞噬百分比,並且降低細胞存活率。在活體試驗中發現,合併處理放射線與三氧化二砷確實可抑制PC-3腫瘤細胞的生長,並且增加LC3Ⅱ與Atg5-Atg12蛋白之表現。綜合以上結果可知,合併處理三氧化二砷可增加放射線對於前列腺癌細胞之效果,並且其所誘發的自體吞噬為經由抑制Akt/mTOR途徑。
英文摘要 Prostate cancer is a leading cause of illness and death among men in the United States and Western Europe. In recent years, the morbidity of prostate cancer in other Asian countries has been also steadily rising. Radiotherapy is one of the treatment for prostate cancer. Many studies indicated that arsenic trioxide (ATO) could enhance the anti-tumor effect of radiotherapy and reduce radiation dosage. The aim of this study was to investigate the anticancer effect of ionizing radiation (IR) combined with arsenic trioxide (ATO) and their underlying mechanisms on prostate cancer LNCaP (wild-type p53) and PC-3 (p53 null) cells. In in vitro study, cell viability was detected by trypan blue. Cell cycle distribution and early apoptosis with annexin V-FITC apoptosis detection kit were analyzed by flow cytometry. In order to observe the expression of acidic vesicular organelle which is characteristic of autophagy, cells were stained with acridine orange. Ultrastructure of PC-3 cells was analyzed by electron microscopy. Western blotting was used to determine apoptosis- and autophagy-associated proteins expression. A nude mice xenograft model was used to investigate the effects of IR combined ATO treatment in vivo. The results indicated that the effect of combined treatment is more significant than IR or ATO alone in LNCaP and PC-3 cells. The combined treatment increased the percentage of apoptosis in LNCaP cells, but did not increase the percentage of apoptosis in PC-3 cells. On the contrary, combined treatment caused cell cycle G2/M arrest in PC-3 cells and increased the percentage of autophagy in both LNCaP and PC-3 cells compared to ATO and IR alone. Furthermore, the expression of LC3Ⅱ and P62/SQSTM1 increased in LNCaP and PC-3 cells treated with combined treatment. The Akt/mTOR pathway was inhibited by combined treatment compared with those subjected to individual treatment. In addition, pretreated with 3-MA, a specific inhibitor of autophagy, decreased the combination-induced autophagy and increased cell viability. Whereas pretreated with LY294002, a specific inhibitor of PI3K/Akt, further enhanced the combination-induced autophagy and decreased cell viability. In in vivo studies, the combination of IR and ATO significantly reduced the tumor volume in nude mice that had received a subcutaneous injection of PC-3 cells. Moreover, the expression of LC3Ⅱand Atg5-Atg12 increased in PC-3 xenograft tumor treated with IR combined with ATO. These results show that combined treatment may increase therapeutic efficacy of prostate cancer cell lines. Moreover, combined treatment induced autophagic cell death through inhibition of Akt/mTOR signaling pathway in LNCaP and PC-3 cells.
論文目次 目錄
第一章、 序論...................................................................................................................1
第二章、 文獻回顧...........................................................................................................2
第一節、 人類前列腺癌(Prostate cancer)與其治療方式.........................................2
第二節、 放射線治療(Radiation therapy)................................................................2
第三節、 三氧化二砷(As2O3)..................................................................................4
第四節、 放射治療合併化學治療...........................................................................5
第五節、 p53.............................................................................................................6
第六節、 細胞週期(Cell cycle).................................................................................7
第七節、 細胞凋亡(Apoptosis)與自體吞噬(Autophagy)........................................9
第三章、 研究目的..........................................................................................................13
第四章、 研究架構..........................................................................................................14
第五章、 研究材料與方法..............................................................................................16
第一節、 研究材料..................................................................................................16
(一) 細胞株......................................................................................................16
(二) 儀器..........................................................................................................17
(三) 試劑與耗材..............................................................................................18
(四) 溶液..........................................................................................................19
第二節、 研究方法..................................................................................................20
(一) 細胞培養與繼代培養..............................................................................20
(二) 細胞解凍..................................................................................................21
(三) 細胞冷凍..................................................................................................21
(四) 細胞計數..................................................................................................22
(五) Clonogenic assay......................................................................................22
(六) 細胞週期分析..........................................................................................22
(七) 早期細胞凋亡分析..................................................................................23
(八) DNA ladder analysis................................................................................23
(九) 活性氧物種(ROS)分析...........................................................................23
(十) Acridine orange免疫螢光染色...............................................................24
(十一) 自體吞噬分析...................................................................................24
(十二) 電子顯微鏡.......................................................................................24
(十三) 西方墨點法(Western blotting)..........................................................25
(十四) BALB/C-nu/nu mice腫瘤誘發實驗.................................................27
(十五) 組織免疫染色(IHC)..........................................................................28
(十六) 統計分析............................................................................................29
第六章、 實驗結果..........................................................................................................30
第一節、 放射線和三氧化二砷對LNCaP細胞與PC-3細胞的劑量與時間效應
....................................................................................................................................30
第二節、 放射線合併三氧化二砷對LNCaP細胞與PC-3細胞的細胞週期變化影響與合併效果......................................................................................31
第三節、 分析合併處理放射線與三氧化二砷對LNCaP細胞與PC-3細胞Apoptosis的表現.....................................................................................32
第四節、 探討合併處理放射線與三氧化二砷對LNCaP細胞與PC-3細胞產生的Autophagy(自體吞噬)現象.................................................................33
第五節、 細胞訊息傳遞路徑之相關蛋白質表現..................................................33
第六節、 腫瘤異體移植活體動物模式..................................................................34
第七章、 討論..................................................................................................................35
第八章、 結論與建議......................................................................................................39
第九章、 參考文獻..........................................................................................................40
圖表....................................................................................................................................49


參考文獻 Abbas, T., Dutta, A., 2009. p21 in cancer: intricate networks and multiple activities. Nat Rev Cancer 9, 400-414.
An, J., Chervin, A.S., Nie, A., Ducoff, H.S., Huang, Z., 2007. Overcoming the radioresistance of prostate cancer cells with a novel Bcl-2 inhibitor. Oncogene 26, 652-661.
Baxter, N.N., Tepper, J.E., Durham, S.B., Rothenberger, D.A., Virnig, B.A., 2005. Increased risk of rectal cancer after prostate radiation: a population-based study. Gastroenterology 128, 819-824.
Bommareddy, A., Hahm, E.R., Xiao, D., Powolny, A.A., Fisher, A.L., Jiang, Y., Singh, S.V., 2009. Atg5 regulates phenethyl isothiocyanate-induced autophagic and apoptotic cell death in human prostate cancer cells. Cancer Res 69, 3704-3712.
Breckenridge, D.G., Xue, D., 2004. Regulation of mitochondrial membrane permeabilization by BCL-2 family proteins and caspases. Curr Opin Cell Biol 16, 647-652.
Cao, C., Subhawong, T., Albert, J.M., Kim, K.W., Geng, L., Sekhar, K.R., Gi, Y.J., Lu, B., 2006. Inhibition of mammalian target of rapamycin or apoptotic pathway induces autophagy and radiosensitizes PTEN null prostate cancer cells. Cancer Res 66, 10040-10047.
Chendil, D., Das, A., Dey, S., Mohiuddin, M., Ahmed, M.M., 2002. Par-4, a pro-apoptotic gene, inhibits radiation-induced NF kappa B activity and Bcl-2 expression leading to induction of radiosensitivity in human prostate cancer cells PC-3. Cancer Biol Ther 1, 152-160.
Cheng, Y., Qiu, F., Tashiro, S., Onodera, S., Ikejima, T., 2008. ERK and JNK mediate TNFalpha-induced p53 activation in apoptotic and autophagic L929 cell death. Biochem Biophys Res Commun 376, 483-488.
Chiu, H.W., Ho, S.Y., Guo, H.R., Wang, Y.J., 2009. Combination treatment with arsenic trioxide and irradiation enhances autophagic effects in U118-MG cells through increased mitotic arrest and regulation of PI3K/Akt and ERK1/2 signaling pathways. Autophagy 5, 472-483.
Chiu, H.W., Lin, J.H., Chen, Y.A., Ho, S.Y., Wang, Y.J., 2010. Combination treatment with arsenic trioxide and irradiation enhances cell-killing effects in human fibrosarcoma cells in vitro and in vivo through induction of both autophagy and apoptosis. Autophagy 6, 353-365.
Colosetti, P., Puissant, A., Robert, G., Luciano, F., Jacquel, A., Gounon, P., Cassuto, J.P., Auberger, P., 2009. Autophagy is an important event for megakaryocytic differentiation of the chronic myelogenous leukemia K562 cell line. Autophagy 5, 1092-1098.
Coward, J., Ambrosini, G., Musi, E., Truman, J.P., Haimovitz-Friedman, A., Allegood, J.C., Wang, E., Merrill, A.H., Jr., Schwartz, G.K., 2009. Safingol (L-threo-sphinganine) induces autophagy in solid tumor cells through inhibition of PKC and the PI3-kinase pathway. Autophagy 5, 184-193.
Damber, J.E., Aus, G., 2008. Prostate cancer. Lancet 371, 1710-1721.
de Bruin, E.C., Medema, J.P., 2008. Apoptosis and non-apoptotic deaths in cancer development and treatment response. Cancer Treat Rev 34, 737-749.
Diaz, R., Nguewa, P.A., Diaz-Gonzalez, J.A., Hamel, E., Gonzalez-Moreno, O., Catena, R., Serrano, D., Redrado, M., Sherris, D., Calvo, A., 2009. The novel Akt inhibitor Palomid 529 (P529) enhances the effect of radiotherapy in prostate cancer. Br J Cancer 100, 932-940.
Dilda, P.J., Hogg, P.J., 2007. Arsenical-based cancer drugs. Cancer Treat Rev 33, 542-564.
Eisenberg-Lerner, A., Bialik, S., Simon, H.U., Kimchi, A., 2009. Life and death partners: apoptosis, autophagy and the cross-talk between them. Cell Death Differ 16, 966-975.
Gao, M., Yeh, P.Y., Lu, Y.S., Hsu, C.H., Chen, K.F., Lee, W.C., Feng, W.C., Chen, C.S., Kuo, M.L., Cheng, A.L., 2008. OSU-03012, a novel celecoxib derivative, induces reactive oxygen species-related autophagy in hepatocellular carcinoma. Cancer Res 68, 9348-9357.
Gewirtz, D.A., Hilliker, M.L., Wilson, E.N., 2009. Promotion of autophagy as a mechanism for radiation sensitization of breast tumor cells. Radiother Oncol 92, 323-328.
Girdhani, S., Bhosle, S.M., Thulsidas, S.A., Kumar, A., Mishra, K.P., 2005. Potential of radiosensitizing agents in cancer chemo-radiotherapy. J Cancer Res Ther 1, 129-131.
Gu, M., Roy, S., Raina, K., Agarwal, C., Agarwal, R., 2009. Inositol hexaphosphate suppresses growth and induces apoptosis in prostate carcinoma cells in culture and nude mouse xenograft: PI3K-Akt pathway as potential target. Cancer Res 69, 9465-9472.
Haimovitz-Friedman, A., 1998. Radiation-induced signal transduction and stress response. Radiat Res 150, S102-108.
Han, Y.H., Moon, H.J., You, B.R., Kim, S.Z., Kim, S.H., Park, W.H., 2010. Effects of arsenic trioxide on cell death, reactive oxygen species and glutathione levels in different cell types. Int J Mol Med 25, 121-128.
Hennessy, B.T., Smith, D.L., Ram, P.T., Lu, Y., Mills, G.B., 2005. Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov 4, 988-1004.
Herman-Antosiewicz, A., Johnson, D.E., Singh, S.V., 2006. Sulforaphane causes autophagy to inhibit release of cytochrome C and apoptosis in human prostate cancer cells. Cancer Res 66, 5828-5835.
Ho, S.Y., Chen, W.C., Chiu, H.W., Lai, C.S., Guo, H.R., Wang, Y.J., 2009. Combination treatment with arsenic trioxide and irradiation enhances apoptotic effects in U937 cells through increased mitotic arrest and ROS generation. Chem Biol Interact 179, 304-313.
Hu, H., Chai, Y., Wang, L., Zhang, J., Lee, H.J., Kim, S.H., Lu, J., 2009. Pentagalloylglucose induces autophagy and caspase-independent programmed deaths in human PC-3 and mouse TRAMP-C2 prostate cancer cells. Mol Cancer Ther 8, 2833-2843.
Jing, Y., Dai, J., Chalmers-Redman, R.M., Tatton, W.G., Waxman, S., 1999. Arsenic trioxide selectively induces acute promyelocytic leukemia cell apoptosis via a hydrogen peroxide-dependent pathway. Blood 94, 2102-2111.
Jung, Y.S., Qian, Y., Chen, X., 2010. Examination of the expanding pathways for the regulation of p21 expression and activity. Cell Signal 22, 1003-1012.
Kang, Y.H., Lee, S.J., 2008. Role of p38 MAPK and JNK in enhanced cervical cancer cell killing by the combination of arsenic trioxide and ionizing radiation. Oncol Rep 20, 637-643.
Kondo, Y., Kanzawa, T., Sawaya, R., Kondo, S., 2005. The role of autophagy in cancer development and response to therapy. Nat Rev Cancer 5, 726-734.
Kondo, Y., Kondo, S., 2006. Autophagy and cancer therapy. Autophagy 2, 85-90.
Kumar, P., Gao, Q., Ning, Y., Wang, Z., Krebsbach, P.H., Polverini, P.J., 2008. Arsenic trioxide enhances the therapeutic efficacy of radiation treatment of oral squamous carcinoma while protecting bone. Mol Cancer Ther 7, 2060-2069.
Lapenna, S., Giordano, A., 2009. Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov 8, 547-566.
Li, Y., Qu, X., Qu, J., Zhang, Y., Liu, J., Teng, Y., Hu, X., Hou, K., Liu, Y., 2009. Arsenic trioxide induces apoptosis and G2/M phase arrest by inducing Cbl to inhibit PI3K/Akt signaling and thereby regulate p53 activation. Cancer Lett 284, 208-215.
Liu, Q., Hilsenbeck, S., Gazitt, Y., 2003. Arsenic trioxide-induced apoptosis in myeloma cells: p53-dependent G1 or G2/M cell cycle arrest, activation of caspase-8 or caspase-9, and synergy with APO2/TRAIL. Blood 101, 4078-4087.
Lu, C., El-Deiry, W.S., 2009. Targeting p53 for enhanced radio- and chemo-sensitivity. Apoptosis 14, 597-606.
Lunghi, P., Tabilio, A., Lo-Coco, F., Pelicci, P.G., Bonati, A., 2005. Arsenic trioxide (ATO) and MEK1 inhibition synergize to induce apoptosis in acute promyelocytic leukemia cells. Leukemia 19, 234-244.
Maiuri, M.C., Tasdemir, E., Criollo, A., Morselli, E., Vicencio, J.M., Carnuccio, R., Kroemer, G., 2009. Control of autophagy by oncogenes and tumor suppressor genes. Cell Death Differ 16, 87-93.
Mathas, S., Lietz, A., Janz, M., Hinz, M., Jundt, F., Scheidereit, C., Bommert, K., Dorken, B., 2003. Inhibition of NF-kappaB essentially contributes to arsenic-induced apoptosis. Blood 102, 1028-1034.
Miller, W.H., Jr., 2002. Molecular targets of arsenic trioxide in malignant cells. Oncologist 7 Suppl 1, 14-19.
Mizushima, N., Yoshimori, T., Levine, B., 2010. Methods in mammalian autophagy research. Cell 140, 313-326.
Murgo, A.J., 2001. Clinical trials of arsenic trioxide in hematologic and solid tumors: overview of the National Cancer Institute Cooperative Research and Development Studies. Oncologist 6 Suppl 2, 22-28.
Neijenhuis, S., Verwijs-Janssen, M., Kasten-Pisula, U., Rumping, G., Borgmann, K., Dikomey, E., Begg, A.C., Vens, C., 2009. Mechanism of cell killing after ionizing radiation by a dominant negative DNA polymerase beta. DNA Repair (Amst) 8, 336-346.
Nelson, W.G., De Marzo, A.M., Isaacs, W.B., 2003. Prostate cancer. N Engl J Med 349, 366-381.
Ning, S., Knox, S.J., 2006. Optimization of combination therapy of arsenic trioxide and fractionated radiotherapy for malignant glioma. Int J Radiat Oncol Biol Phys 65, 493-498.
Palayoor, S.T., Bump, E.A., Calderwood, S.K., Bartol, S., Coleman, C.N., 1998. Combined antitumor effect of radiation and ibuprofen in human prostate carcinoma cells. Clin Cancer Res 4, 763-771.
Parikh, A., Childress, C., Deitrick, K., Lin, Q., Rukstalis, D., Yang, W., 2010. Statin-induced autophagy by inhibition of geranylgeranyl biosynthesis in prostate cancer PC3 cells. Prostate 70, 971-981.
Peng, P.L., Kuo, W.H., Tseng, H.C., Chou, F.P., 2008. Synergistic tumor-killing effect of radiation and berberine combined treatment in lung cancer: the contribution of autophagic cell death. Int J Radiat Oncol Biol Phys 70, 529-542.
Pilepich, M.V., Winter, K., Lawton, C.A., Krisch, R.E., Wolkov, H.B., Movsas, B., Hug, E.B., Asbell, S.O., Grignon, D., 2005. Androgen suppression adjuvant to definitive radiotherapy in prostate carcinoma--long-term results of phase III RTOG 85-31. Int J Radiat Oncol Biol Phys 61, 1285-1290.
Pruschy, M., Resch, H., Shi, Y.Q., Aalame, N., Glanzmann, C., Bodis, S., 1999. Ceramide triggers p53-dependent apoptosis in genetically defined fibrosarcoma tumour cells. Br J Cancer 80, 693-698.
Puissant, A., Robert, G., Fenouille, N., Luciano, F., Cassuto, J.P., Raynaud, S., Auberger, P., 2010. Resveratrol promotes autophagic cell death in chronic myelogenous leukemia cells via JNK-mediated p62/SQSTM1 expression and AMPK activation. Cancer Res 70, 1042-1052.
Ren, Y., Xie, Y., Chai, L., Wang, S., Cheng, M., 2010. Autophagy modification augmented the treatment effects initiated by arsenic trioxide in NB4 cells. Med Oncol.
Ricci, M.S., Zong, W.X., 2006. Chemotherapeutic approaches for targeting cell death pathways. Oncologist 11, 342-357.
Roboz, G.J., Dias, S., Lam, G., Lane, W.J., Soignet, S.L., Warrell, R.P., Jr., Rafii, S., 2000. Arsenic trioxide induces dose- and time-dependent apoptosis of endothelium and may exert an antileukemic effect via inhibition of angiogenesis. Blood 96, 1525-1530.
Ronit Vogt Sionov, I.L.H., Ygal Haupt The Regulation of p53 Growth Suppression. Madame Curie Bioscience Database, cell cycle.
Shimizu, S., Konishi, A., Nishida, Y., Mizuta, T., Nishina, H., Yamamoto, A., Tsujimoto, Y., 2010. Involvement of JNK in the regulation of autophagic cell death. Oncogene 29, 2070-2082.
Shinojima, N., Yokoyama, T., Kondo, Y., Kondo, S., 2007. Roles of the Akt/mTOR/p70S6K and ERK1/2 signaling pathways in curcumin-induced autophagy. Autophagy 3, 635-637.
Shintani, T., Klionsky, D.J., 2004. Autophagy in health and disease: a double-edged sword. Science 306, 990-995.
Smith, D.M., Patel, S., Raffoul, F., Haller, E., Mills, G.B., Nanjundan, M., 2010. Arsenic trioxide induces a beclin-1-independent autophagic pathway via modulation of SnoN/SkiL expression in ovarian carcinoma cells. Cell Death Differ.
Su, L.N., Little, J.B., 1993. Prolonged cell cycle delay in radioresistant human cell lines transfected with activated ras oncogene and/or simian virus 40 T-antigen. Radiat Res 133, 73-79.
Suh, Y., Afaq, F., Khan, N., Johnson, J.J., Khusro, F.H., Mukhtar, H., 2010. Fisetin induces autophagic cell death through suppression of mTOR signaling pathway in prostate cancer cells. Carcinogenesis.
Sumi, D., Shinkai, Y., Kumagai, Y., 2010. Signal transduction pathways and transcription factors triggered by arsenic trioxide in leukemia cells. Toxicol Appl Pharmacol 244, 385-392.
Szostak, M.J., Kyprianou, N., 2000. Radiation-induced apoptosis: predictive and therapeutic significance in radiotherapy of prostate cancer (review). Oncol Rep 7, 699-706.
Tasdemir, E., Maiuri, M.C., Galluzzi, L., Vitale, I., Djavaheri-Mergny, M., D'Amelio, M., Criollo, A., Morselli, E., Zhu, C., Harper, F., Nannmark, U., Samara, C., Pinton, P., Vicencio, J.M., Carnuccio, R., Moll, U.M., Madeo, F., Paterlini-Brechot, P., Rizzuto, R., Szabadkai, G., Pierron, G., Blomgren, K., Tavernarakis, N., Codogno, P., Cecconi, F., Kroemer, G., 2008a. Regulation of autophagy by cytoplasmic p53. Nat Cell Biol 10, 676-687.
Tasdemir, E., Maiuri, M.C., Orhon, I., Kepp, O., Morselli, E., Criollo, A., Kroemer, G., 2008b. p53 represses autophagy in a cell cycle-dependent fashion. Cell Cycle 7, 3006-3011.
Uslu, R., Sanli, U.A., Sezgin, C., Karabulut, B., Terzioglu, E., Omay, S.B., Goker, E., 2000. Arsenic trioxide-mediated cytotoxicity and apoptosis in prostate and ovarian carcinoma cell lines. Clin Cancer Res 6, 4957-4964.
Verrier, F., Deniaud, A., Lebras, M., Metivier, D., Kroemer, G., Mignotte, B., Jan, G., Brenner, C., 2004. Dynamic evolution of the adenine nucleotide translocase interactome during chemotherapy-induced apoptosis. Oncogene 23, 8049-8064.
Wayne M. Becker, L.J.K., Jeff Hardin & Gregory P. Bertoni, 2009. The World of the Cell, 7th Edition.
Wu, W.K., Cho, C.H., Lee, C.W., Wu, Y.C., Yu, L., Li, Z.J., Wong, C.C., Li, H.T., Zhang, L., Ren, S.X., Che, C.T., Wu, K., Fan, D., Yu, J., Sung, J.J., 2010. Macroautophagy and ERK phosphorylation counteract the antiproliferative effect of proteasome inhibitor in gastric cancer cells. Autophagy 6, 228-238.
Xie, L.X., Lin, X.H., Li, D.R., Chen, J.Y., Hong, C.Q., Du, C.W., 2007. Synergistic therapeutic effect of arsenic trioxide and radiotherapy in BALB/C nude mice bearing nasopharyngeal carcinoma xenografts. Exp Oncol 29, 45-48.
Yang, Y.P., Liang, Z.Q., Gao, B., Jia, Y.L., Qin, Z.H., 2008. Dynamic effects of autophagy on arsenic trioxide-induced death of human leukemia cell line HL60 cells. Acta Pharmacol Sin 29, 123-134.
Yoda, A., Toyoshima, K., Watanabe, Y., Onishi, N., Hazaka, Y., Tsukuda, Y., Tsukada, J., Kondo, T., Tanaka, Y., Minami, Y., 2008. Arsenic trioxide augments Chk2/p53-mediated apoptosis by inhibiting oncogenic Wip1 phosphatase. J Biol Chem 283, 18969-18979.
Zhuang, W., Qin, Z., Liang, Z., 2009. The role of autophagy in sensitizing malignant glioma cells to radiation therapy. Acta Biochim Biophys Sin (Shanghai) 41, 341-351.
Zois, C.E., Koukourakis, M.I., 2009. Radiation-induced autophagy in normal and cancer cells: towards novel cytoprotection and radio-sensitization policies? Autophagy 5, 442-450.
論文全文使用權限
  • 同意授權校內瀏覽/列印電子全文服務,於2015-08-17起公開。


  • 如您有疑問,請聯絡圖書館
    聯絡電話:(06)2757575#65773
    聯絡E-mail:etds@email.ncku.edu.tw