BV6, an IAP antagonist, activates apoptosis and enhances radiosensitization of non-small cell lung carcinoma in vitro.
BV6, an IAP antagonist, activates apoptosis and enhances radiosensitization of non-small cell lung carcinoma in vitro.
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DOI：
10.1097/jto.0b013e318226b4a6
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发表时间：
2011-11
期刊：
影响因子：
--
通讯作者：
Lu B
中科院分区：
文献类型：
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作者：
Li W;Li B;Giacalone NJ;Torossian A;Sun Y;Niu K;Lin-Tsai O;Lu B
细胞凋亡途径的缺陷限制了放射治疗在非小细胞肺癌（NSCLC）治疗中的有效性。BV 6是凋亡抑制剂（inhibitors of apoptosis，IAP）家族成员cIAP 1和XIAP的拮抗剂。我们研究了BV 6使NSCLC细胞系对辐射敏感的潜力。用BV 6处理HCC 193和H460肺癌细胞系，以研究给药对细胞增殖、凋亡、XIAP和cIAP 1抑制以及放射敏感性的影响。随后的免疫印迹和Hoechst染色用于确定细胞凋亡在放射增敏中的作用。最后，通过Western印迹分析裂解的caspase-8和裂解的caspase-9，以及ELISA测定TNF-α来表征凋亡途径。HCC 193细胞对BV 6诱导的细胞凋亡的敏感性高于H460细胞，且呈浓度依赖性和时间依赖性。BV 6显著地使两种细胞系对辐射敏感（HCC 193-DER=1.38，在1μM BV 6时p<0.05; H460-DER=1.42，在5μM BV 6时p<0.05），但是对于H460细胞，需要更高浓度的BV 6和更长的孵育时间。BV 6诱导的HCC 193的放射增敏作用有利于细胞凋亡的外源性途径，而H460则有利于细胞凋亡的内源性途径。IAP拮抗剂BV 6在体外可显著增强HCC 193和H460细胞的放射增敏作用。需要更多的研究来测试BV 6的作用机制，并评估其在体内和临床环境中的潜力。
Defects in the apoptosis pathway limit the effectiveness of radiation in non-small cell lung cancer (NSCLC) therapy. BV6 is an antagonist of cIAP1 and XIAP, members of the inhibitors of apoptosis (IAP) family. We investigated the potential of BV6 to sensitize NSCLC cell lines to radiation. HCC193 and H460 lung cancer cell lines were treated with BV6 to investigate the effects of drug administration on cell proliferation, apoptosis, inhibition of XIAP and cIAP1, and radiosensitivity. Subsequent immunoblotting and Hoechst staining were utilized to determine the role of apoptosis in radiosensitization. Finally, the pathway of apoptosis was characterized by western blot analysis for cleaved caspase-8 and cleaved caspase-9, and ELISA assays for TNF-α. HCC193 was found to be more sensitive than H460 to BV6-induced apoptosis in a concentration-dependent and time-dependent manner. BV6 significantly sensitized both cell lines to radiation (HCC193—DER=1.38, p<0.05 at 1μM BV6; H460—DER=1.42, p<0.05 at 5μM BV6), but a higher concentration of and longer incubation time with BV6 was necessary for H460 cells. The BV6-induced radiosensitization of HCC193 favored the extrinsic pathway of apoptosis, while that of H460 favored the intrinsic pathway. BV6, an IAP antagonist, significantly enhanced the radiosensitization of HCC193 and H460 cells in vitro. More research is warranted to test the mechanism of action of BV6, and to assess its potential in vivo and in the clinical setting.