Kosaka Takeo, Hongo Hiroshi, Miyazaki Yasumasa, Nishimoto Koshiro, Miyajima Akira, Oya Mototsugu
Department of Urology, Keio University School of Medicine, Tokyo, Japan.
Department of Uro-Oncology, Saitama Medical University International Medical Center, Hidaka, Japan.
Oncotarget. 2017 Sep 21;8(50):87675-87683. doi: 10.18632/oncotarget.21147. eCollection 2017 Oct 20.
Reactive oxygen species (ROS) production induced by taxanes in cancer cells may influence the taxane-induced cell death or the drug resistance. We investigated the correlation between the cytotoxic effect of taxanes and ROS production in human castration-resistant prostate cancer (CRPC) cell lines. Three human prostate cancer cell lines were treated with increasing concentrations of docetaxel or cabazitaxel . Cabazitaxel showed significantly higher cytotoxic efficacy than docetaxel in human CRPC cells, accompanied by elevated ROS production detected by FACS analysis. To investigate whether cabazitaxel-mediated cell death was caused by the ROS generation induced by cabazitaxel, we treated CRPC cells in the presence of antioxidant NAC. NAC reduced the cytotoxic effect induced by cabazitaxel. We found that ROS elimination by Sestrin-3 () was significantly inhibited by cabazitaxel, but not by docetaxel. These results indicate higher sensitivity of human CRPC to cabazitaxel compared to docetaxel involves ROS production through inhibiting the expression of antioxidant enzyme SESN3.
紫杉烷在癌细胞中诱导产生的活性氧（ROS）可能会影响紫杉烷诱导的细胞死亡或耐药性。我们研究了紫杉烷的细胞毒性作用与人类去势抵抗性前列腺癌（CRPC）细胞系中ROS产生之间的相关性。用递增浓度的多西他赛或卡巴他赛处理三种人类前列腺癌细胞系。在人类CRPC细胞中，卡巴他赛显示出比多西他赛显著更高的细胞毒性效力，同时通过流式细胞术分析检测到ROS产生增加。为了研究卡巴他赛介导的细胞死亡是否由卡巴他赛诱导的ROS生成引起，我们在抗氧化剂NAC存在的情况下处理CRPC细胞。NAC降低了卡巴他赛诱导的细胞毒性作用。我们发现，卡巴他赛可显著抑制Sestrin-3（）介导的ROS清除，但多西他赛无此作用。这些结果表明，与多西他赛相比，人类CRPC对卡巴他赛的更高敏感性涉及通过抑制抗氧化酶SESN3的表达来产生ROS。
