15-deoxy-Δ12, 14prostaglandin J2 enhances anticancer activities independently of VHL status in renal cell carcinomas
15-deoxy-Δ12, 14prostaglandin J2 enhances anticancer activities independently of VHL status in renal cell carcinomas
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DOI：
10.1016/j.bbrep.2019.01.001
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发表时间：
2019-07-01
影响因子：
2.7
通讯作者：
Yagami，Tatsurou
中科院分区：
文献类型：
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作者：
Koma，Hiromi;Yamamoto，Yasuhiro;Yagami，Tatsurou
肾细胞癌（RCC）相对耐化疗和放疗。透明细胞RCC （ccRCC）占RCC的大多数，这些RCC具有von Hippel-Lindau （VHL）基因突变或表观遗传沉默。vhl阳性的Caki-2细胞被内源性抗癌物质15-脱氧-Δ12, 14-前列腺素J2（15d-PGJ2）杀死。采用反映线粒体琥珀酸脱氢酶活性的MTT还原法评估细胞活力。我们证实喜树碱（拓扑异构酶I抑制剂）、依托泊苷（拓扑异构酶II抑制剂）、阿霉素（拓扑异构酶II抑制剂）在vhl阳性的Caki-2细胞中具有抗癌活性。拓扑异构酶抑制剂与15d- pgj22联合使用在vhl阳性的Caki-2细胞中表现出协同作用。然而，15d- pgj22并没有增加拓扑异构酶抑制剂对vhl -阴性786-O细胞的细胞毒性。此外，在vhl阳性和vhl阴性的RCC4细胞中均未检测到15d- pgj2增强的拓扑异构酶抑制剂的抗肿瘤活性。我们的研究结果表明，15d- pgj22可以独立于VHL增强拓扑异构酶抑制剂的抗肿瘤活性。
Renal cell carcinoma (RCC) is relatively resistant to chemotherapy and radiotherapy. Clear cell RCC (ccRCC) accounts for the majority of RCC, which have mutations or epigenetic silencing of thevon Hippel–Lindau(VHL) gene. VHL-positive Caki-2 cells are killed by an endogenous anticancer substance, 15-deoxy-Δ12, 14-prostaglandin J2(15d-PGJ2). The MTT reduction assay reflecting mitochondrial succinate dehydrogenase activity was employed for assessment of cell viability. We confirmed anticancer activities of camptothecin (topoisomerase I inhibitor), etoposide (topoisomerase II inhibitor), doxorubicin (topoisomerase II inhibitor) in VHL-positive Caki-2 cells. Combination of topoisomerase inhibitors with 15d-PGJ2exhibited the synergistic effect in VHL-positive Caki-2 cells. However, 15d-PGJ2did not increase cytotoxicities of topoisomerase inhibitors on VHL-negative 786-O cells. In addition, the 15d-PGJ2-enhanced antitumor activity of topoisomerase inhibitors was detected in neither VHL-positive nor VHL-negative RCC4 cells. Our finding indicated that 15d-PGJ2enhanced the antitumor activity of topoisomerase inhibitors independently of VHL.