Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 2-1, Kami-ohno 7-Chome, Himeji, Hyogo 670-8524, Japan.
Biochem Biophys Res Commun. 2011 Jul 8;410(3):563-7. doi: 10.1016/j.bbrc.2011.06.026. Epub 2011 Jun 12.
Renal cell carcinoma (RCC) is chemoresistant cancer. Although several clinical trials were conducted to explore effective medications, the chemoresistance of RCC has not yet been conquered. An endogenous ligand for peroxisome proliferator-activated receptor-γ (PPARγ), 15-deoxy-Δ(12,14)-prostaglandin J(2) (15d-PGJ(2)), induces apoptosis in RCC. Here, we examined synergistic effects of several carcinostatics on the anti-tumor activity of 15d-PGJ(2) in Caki-2 cell line by MTT assay. A topoisomerase-I inhibitor, camptothecin (CPT), exhibited synergistically toxicity with 15d-PGJ(2), but neither 5-fluorouracil nor cisplatin did. The combination of 15d-PGJ(2) and a topoisomerase-II inhibitor, doxorubicine, did not cause synergistic cell growth inhibition. The synergistic effect of topoisomerase-I and II inhibitors was not also detected. A PPARγ antagonist, GW9662, did not prevent Caki-2 from undergoing 15d-PGJ(2)-induced cytotoxicity. The treatment of CPT combined with 15d-PGJ(2) activated caspase-3 more than the separate treatment. These results suggest that 15d-PGJ(2) exhibited the anti-tumor activity synergistically with CPT independent of topoisomerase-II and PPARγ.
肾细胞癌（RCC）是一种化疗耐药的癌症。尽管进行了几项临床试验来探索有效的药物，但 RCC 的化疗耐药性尚未得到克服。过氧化物酶体增殖物激活受体-γ（PPARγ）的内源性配体 15-脱氧-Δ（12,14）-前列腺素 J2（15d-PGJ2）诱导 RCC 细胞凋亡。在这里，我们通过 MTT 测定法检查了几种抗癌药对 Caki-2 细胞系中 15d-PGJ2 抗肿瘤活性的协同作用。拓扑异构酶 I 抑制剂喜树碱（CPT）与 15d-PGJ2 表现出协同毒性，但 5-氟尿嘧啶和顺铂则没有。15d-PGJ2 和拓扑异构酶 II 抑制剂阿霉素的联合使用并未导致协同的细胞生长抑制。也未检测到拓扑异构酶 I 和 II 抑制剂的协同作用。PPARγ 拮抗剂 GW9662 不能阻止 Caki-2 发生 15d-PGJ2 诱导的细胞毒性。CPT 联合 15d-PGJ2 治疗比单独治疗更能激活 caspase-3。这些结果表明，15d-PGJ2 与 CPT 联合表现出与拓扑异构酶 II 和 PPARγ 无关的抗肿瘤活性。
