WP1130对宫颈鳞癌细胞顺铂化疗增敏性的分析

目的:探索X染色体连锁的泛素特异肽酶9（ubiquitin-specific peptidase 9 X-linked，USP9X）抑制剂WP1130在宫颈鳞癌细胞中对顺铂（diaminodichloroplatin，DDP）化疗敏感性的影响。方法:CCK8筛选DDP及WP1130作用于SiHa细胞的最佳浓度剂量,并研究DDP与WP1130联用对SiHa细胞抑制率的影响；免疫细胞化学（immunocytochemistry,ICC）方法检测WP1130对SiHa细胞USP9X表达的影响；Western blot方法检测药物作用前后USP9X蛋白的表达水平，并探讨WP1130对SiHa细胞顺铂化疗敏感性的影响。结果:CCK8筛选的3 μg/ml DDP及1.5 μmol/L WP1130作用于SiHa 细胞72 h为最佳剂量， WP1130联合DDP组SiHa细胞的存活率较单用DDP组显著降低（P＜0.05）；ICC显示WP1130可抑制USP9X蛋白的表达；Western blot发现SiHa细胞中USP9X蛋白的表达水平在DDP及WP1130作用后降低（P＜0.05），且在DDP联用WP1130组中最低（P＜0.05）。结论:WP1130能增强宫颈鳞癌细胞对DDP的敏感性，可为宫颈鳞癌综合治疗提供有力依据。

WP1130 incereases sensitivity to cis-platinum in cervical squamous-cell carcinoma(CSCC) cell

Objective:To observe the effect of incereased sensitivity to cis-platinum in SiHa by USP9X inhibitor WP1130 in order to provide a theoretical basis for seeking therapeutic target of CSCC.Methods:The optimal concentration of cis-platinum and WP1130 effected on SiHa were screened by CCK8.The effects of different concentrations of cis-platinum,cis-platinum together with WP1130 on the inhibition rate of SiHa cells were studied.The effect of WP1130 on the expression of USP9X in SiHa cells was detected by immunocytochemistry.The protein expressions of USP9X before and after chemical drug in SiHa were detected by Western blot and the sensitivity of WP1130 to SiHa cells was also studied.Results:The optimal concentration of cis-platinum was 3 μg/ml and WP1130 was 1.5 μmol/L,both treated 72 hours in SiHa.The survival rate decreased significantly in SiHa treated with cis-platinum and WP1130 compared with cis-platinum alone(P＜0.05).Immunocytochemistry showed WP1130 could inhibit the expression of USP9X protein.The protein expressions of USP9X was significantly reduced in SiHa treated with 3 μg/ml cis-platinum or（and) 1.5 μmol/L WP1130(P＜0.05) and the protein level in SiHa which treated with cis-platinum combined with WP1130 was less than cis-platinum or WP1130 alone(P＜0.05).Conclusion:WP1130 sensitized CSCC to cis-platinum,providing strong basis for the clinical integrated treatment of cervical carcinoma.