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肿瘤坏死因子相关诱导凋亡配体联合化疗药物治疗膀胱癌的研究 被引量:5

Experimental study on treatment of bladder cancer with a combination of TRAIL and chemotherapeutic agents
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摘要 目的 探讨肿瘤坏死因子相关诱导凋亡配体 (TRAIL)治疗膀胱肿瘤的作用 ,以及与化疗药物的协同作用。方法 将T2 4及 5 63 7膀胱肿瘤细胞接种至 96孔培养板后分别加入浓度为1、10、10 0 μg/L的TRAIL ,0 .1、1.0、10 .0mg/L的阿霉素 (ADM )和丝裂霉素 (MMC) ,不同浓度的TRAIL、ADM、TRAIL和MMC ,噻唑蓝比色 (MTT)法分别检测肿瘤细胞的生存率。将膀胱肿瘤细胞接种至 12孔板 ,培育 2 4h后加入不同浓度的TRAIL、ADM、MMC、TRAIL联合ADM、MMC。用流式细胞术检测不同处理组肿瘤细胞的凋亡率和死亡率。结果  10 0 μg/LTRAIL引起T2 4、5 63 7细胞的凋亡率分别为 2 0 .1%、45 .3 % ,与无药物组 1.1%、3 .5 %的凋亡率比较差异有非常显著性(P <0 .0 1)。单独运用 10mg/LMMC、ADM对T2 4、5 63 7的抑制率分别为 3 6.0 %、44 .1%、2 6.7%、3 0 .2 % ;而 10 0 μg/LTRAIL和 10mg/LMMC、ADM联合后对T2 4、5 63 7的抑制率分别达到 5 8.4%、73 .7%、90 .7%、88.2 % ,两者有明显的协同作用 (P <0 .0 5 )。结论 在体外实验中 ,TRAIL可通过诱导肿瘤细胞的凋亡而产生抗膀胱肿瘤的作用 ;TRAIL与化疗药物ADM。 Objective To explore the role of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and the effect of TRAIL combined with chemotherapeutic agents in treatment of bladder cancer.Methods T24 and 5637 bladder cancer cell lines were employed in our study.100μl of target cell suspension were added to each well of 96-well plates.The bladder cancer cells were incubated for 24 hours with TRAIL,Adriamycin,MitomycinC and TRAIL combined with chemotherapeutic agents at different concentration。MTT working solution was added to each culture well and calculated the survival rates of bladder cancer cells.Bladder cancer cell suspension was added to 12-well plates,then incubated for 12 hours with TRAIL,Adriamycin,Mitomycin and TRAIL combined with chemotherapeutic agents at different concentration.The rates of apoptosis and death of bladder cancer cells were detected by flow cytometry.Results The rates of apoptosis of bladder cancer cell T24、5637 were 20.1%、47.5% by treated with 100 μg/l TRAIL singly,which had significant difference compared with the groups without agents(P<0.01);The inhibitory rates of T24、5637 were 36.0%、44.1%、26.7%、30.2% by treated with 10 mg/L MMC、ADM.However the inhibitory rates reached 58.4%、73.7%、90.7%、88.2% by 100 μg/l TRAIL combined with 10 mg/L MMC、ADM in T24 and 5637.Combinations of TRAIL and MMC,TRAIL and ADM resulted in a synergistic cytotoxic effect (P<0.05).Conclusions In vitro,TRAIL is an agent for anti-bladder cancer by inducing the apoptosis of tumor cell ;TRAIL can enhance the effect of Adriamycin and Mitomycin C.
出处 《中华实验外科杂志》 CAS CSCD 北大核心 2003年第9期840-842,共3页 Chinese Journal of Experimental Surgery
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同被引文献33

  • 1谭毓治,万晓霞,赖娟娟,陈慧敏.葡萄籽原花青素对学习记忆的影响[J].中国药理学通报,2004,20(7):804-807. 被引量:26
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  • 3Zhang Y,Ma CH,Liu H,et al. pVAX1 plasmid vector-mediated gene transfer of soluble TRAIL suppresses human hepatocellular carcinoma growth in nude mice. Acta Biochim Pol,2007,54:307-313.
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  • 6Naumann U, Waltereit R, Schulz JB, et al. Adenoviral (full-length) Apo2L/TRAIL gene transfer is an ineffective treatment strategy for malignant glioma. J Neurooncol,2003,61:7-15.
  • 7Gliniak B ,Le T. Tumor necrosis factor-related apoptosis-inducing ligand' s antitumor activity in vivo is enhanced by the chemotherapeutic agent CPT-11. Cancer Res, 1999,59:6153-6158.
  • 8Jazirehi AR, Ng CP, Gan XH, et al. Adriamyein sensitizes the adriamycin-resistant 8226/Dox40 human multiple myeloma cells to Apo2L/tumor necrosis factor-related apoptosis-inducing ligand-mediated(TRAIL) apoptosis. Clin Cancer Res,2001,7 :3874-3883.
  • 9Mizutani Y, Nakanishi H, Yoshida O, et al. Potentiation of the sensitivity of renal cell carcinoma cells to TRAIL-mediated apoptosis by subtoxic concentrations of 5-fluorouracil. Eur J Cancer,2002,38 : 167- 176.
  • 10Shankar S, Chen X, Srivastava RK. Effects of sequential treatments with chemotherapeutic drugs folIowed by TRAIL on prostate cancer in vitro and in vivo. Prostate,2005,62:165-186.

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