Up-regulation of ICH-1L protein by thromboxane A2 antagonists enhances cisplatin-induced apoptosis in non-small-cell lung-cancer cell lines
Up-regulation of ICH-1L protein by thromboxane A2 antagonists enhances cisplatin-induced apoptosis in non-small-cell lung-cancer cell lines
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DOI：
10.1007/s004320050291
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发表时间：
1999-07-01
影响因子：
3.6
通讯作者：
Matsuda, T
中科院分区：
文献类型：
--
作者：
Fujimura, M;Kasahara, K;Matsuda, T
我们评估了血栓素A（2）（TXA（2））阻断剂对顺铂诱导的非小细胞肺癌（NSCLC）细胞系凋亡的影响。顺铂以剂量依赖方式诱导PC/9和PC-9/CDDP细胞凋亡。用特异性TXA（2）拮抗剂5（Z）-1R，2S，3S，4S-7-[3-苯磺酰基氨基双环[2.2.1]庚-2-基]-5-庚酸钙水合物（S-1452）和5（Z-6-{（1R，2R，3R，4S）-3-（N-4-溴苯磺酰氨基甲基）二环[2，2，1]庚烷-2-基）己-5-烯酸（ONO-NT-126）增强顺铂诱导的每个细胞系的凋亡。乙酰-L-谷氨酰-缬氨酰-门冬氨酸-1-醛（Ac-DEVD-CHO）抑制顺铂诱导的细胞凋亡和TXA（2）阻断对细胞凋亡的促进作用，而乙酰-L-酪氨酰-缬氨酰-丙氨酰-门冬氨酸-1-醛（Ac-YVAD-CHO）对细胞凋亡无影响。在两种细胞系中，白细胞介素-1 β转化酶（ICE）蛋白酶蛋白表达无差异。半胱氨酸蛋白酶p32（CPP 32）蛋白表达在PC-9/CBDP中较低，但不受S-1452、顺铂的影响。或与顺铂和S-1452联合治疗。Ice和Ced-3同源物（ICH-IL）表达在PC-9/CDDP中显著降低，并被S-1452或ONO-NT-126上调。这些数据表明，ICH-1 L可能在顺铂诱导的细胞凋亡中起关键作用，TXA（2）阻断剂上调ICH-1 L蛋白表达。ICH-1 L过表达和顺铂治疗可能导致NSCLC细胞系凋亡增加。
We evaluated the effect of thromboxane A(2) (TXA(2)) blockade on cisplatin-induced apoptosis in nonsmall-cell lung cancer (NSCLC) cell lines. Cisplatin induced apoptosis in PC/9 and PC-9/CDDP in a dose-dependent manner. Treatment with specific TXA(2) antagonist, calcium 5(Z)-1R,2S,3S,4S-7-[3-phenylsulfonylaminobicyclo[2.2.1]hept-2-yl]-5-heptonoate hydrate (S-1452) and 5(Z-6-{(1R,2R,3R,4S)-3-(N-4-bromobenzenesulfonyl aminomethyl) bicyclo[2,2,1]heptane-2-yl)hex-5-enoic acid (ONO-NT-126), enhanced the cisplatin-induced apoptosis in each cell line. Acetyl-L-aspartyl-glutamyl-valyl-aspart-1-aldehyde (Ac-DEVD-CHO) inhibited cisplatin-induced apoptosis and enhancement of the apoptosis by TXA(2) blockade, but acetyl-L-tyrosyl-valyl-alanyl-aspart-1-aldehyde (Ac-YVAD-CHO) had no effect on the apoptosis. There was no difference in the interleukin-1 beta-converting enzyme (ICE) protease protein expression in either cell line. Cysteine protease p32(CPP32) protein expression was lower in PC-9/CBDP but was not changed by S-1452, cisplatin. or cotreatment with cisplatin and S-1452. Ice and Ced-3 homolog (ICH-IL) expression was significantly lower in PC-9/CDDP and was up-regulated by S-1452 or ONO-NT-126. These data suggest that ICH-1L might play a critical role in cisplatin-induced apoptosis and that TXA(2) blockade up-regulates ICH-1L protein expression. Overexpression of ICH-1L and treatment with cisplatin might result in an increase is apoptosis in NSCLC cell lines.