Miyamoto Morikazu, Takano Masashi, Aoyama Tadashi, Soyama Hiroaki, Ishibashi Hiroki, Kato Kento, Iwahashi Hideki, Takasaki Kazuki, Kuwahara Mika, Matuura Hiroko, Sakamoto Takahiro, Yoshikawa Tomoyuki, Furuya Kenichi
Department of Obstetrics and Gynecology, National Defense Medical College Hospital, Tokorozawa, Japan
Department of Clinical Oncology, National Defense Medical College Hospital, Tokorozawa, Japan.
Anticancer Res. 2018 Jan;38(1):301-306. doi: 10.21873/anticanres.12222.
BACKGROUND/AIM: To investigate whether XIAP down-regulation and autophagy inhibition sensitize ovarian clear cell cancer cells to cisplatin.
The ovarian clear cancer cell line KK was used for in vitro analysis. Hydroxychloroquine (HCQ) and phenoxodiol (PXD) or embelin were used as autophagy and XIAP inhibitors, respectively. Non-specific and XIAP-specific siRNAs were transfected using Lipofectamine. Cytotoxicity was assessed by MTT assays. Protein expression was confirmed by western blotting.
In KK, down-regulation of XIAP using specific siRNAs together with HCQ treatment enhanced the anti-tumor effect of cisplatin. Although embelin sensitized KK to cisplatin through XIAP down-regulation, it induced autophagy. However, PXD increased cisplatin sensitivity through XIAP down-regulation and autophagy inhibition. Expression of Atg7, Atg12, and Beclin 1 was decreased after PXD treatment.
PXD increased cisplatin sensitivity through XIAP down-regulation and autophagy inhibition and could be a new candidate for ovarian clear cell carcinoma treatment.
背景/目的：探讨下调X连锁凋亡抑制蛋白（XIAP）和抑制自噬是否能使卵巢透明细胞癌细胞对顺铂敏感。
采用卵巢透明癌细胞系KK进行体外分析。分别使用羟氯喹（HCQ）和苯氧二醇（PXD）或紫铆因作为自噬抑制剂和XIAP抑制剂。使用脂质体转染非特异性和XIAP特异性小干扰RNA（siRNA）。通过MTT法评估细胞毒性。通过蛋白质免疫印迹法确认蛋白质表达。
在KK细胞中，使用特异性siRNA下调XIAP并联合HCQ处理可增强顺铂的抗肿瘤作用。虽然紫铆因通过下调XIAP使KK细胞对顺铂敏感，但它会诱导自噬。然而，PXD通过下调XIAP和抑制自噬增加了顺铂敏感性。PXD处理后，自噬相关蛋白7（Atg7）、自噬相关蛋白12（Atg12）和Beclin 1的表达降低。
PXD通过下调XIAP和抑制自噬增加了顺铂敏感性，可能成为治疗卵巢透明细胞癌的新候选药物。
