CTHRC1对卵巢癌细胞顺铂耐药的作用及机制研究

目的:探究胶原三股螺旋重复蛋白1(CTHRC1)对卵巢癌细胞顺铂耐药的作用及其相关机制。方法:Western blot法检测卵巢癌细胞株A2780、SKOV3及顺铂耐药细胞株A2780/DDP、SKOV3/DDP中CTHRC1蛋白表达水平。慢病毒lenti-sh CTHRC1转染SKOV3/DDP细胞,下调CTHRC1表达水平。CCK-8法检测沉默CTHRC1后SKOV3/DDP细胞增殖情况及顺铂半数抑制浓度(IC_(50))的变化。Western blot法检测转染后SKOV3/DDP细胞中抗凋亡蛋白Bcl-2的表达情况及Akt、STAT3的磷酸化水平。结果:与A2780和SKOV3细胞相比,顺铂耐药细胞株A2780/DDP和SKOV3/DDP细胞中CTHRC1蛋白表达水平相对较高(P0.05)。靶向下调CTHRC1表达后,SKOV3/DDP-sh CTHRC1细胞的增殖能力无明显变化,但顺铂的IC_(50)显著降低(P0.01),Akt、STAT3磷酸化水平受到抑制,Bcl-2表达水平降低(P0.05)。结论:CTHRC1可能通过Akt、STAT3信号通路,调节抗凋亡蛋白Bcl-2的表达,继而影响卵巢癌细胞对顺铂的敏感度。

The role of CTHRC1 in cisplatin-resistance of ovarian cancer cells and related mechanisms

Objective:To determine the effect of collagen triple helix repeat containing-1 (CTHRC1) on cisplatin-resistance of ovarian cancer cells and related mechanisms.Methods:The expression of CTHRC1 in A2780、A2780/DDP、SKOV3、SKOV3/DDP cells was detected by Western blot.SKOV3/DDP cells were transfected with lenti-shCTHRC1 to down-regulate CTHRC1.Then CCK-8 kit was used to investigate the capability of proliferation and the half-cell lethal dose (IC50) of cisplatin.The expression of Bcl-2,p-STAT3,p-Akt were assessed by Western blot.Result:The expression of CTHRC1 in A2780、SKOV3 cells was lower than that in A2780/DDP、SKOV3/DDP cells (P<0.05).Down-regulation of CTHRC1 had no influence on the proliferation of SKOV3/DDP cells,however,it cloud significantly decreased the IC50 of cisplatin in SKOV3/DDP cells (P<0.01).Meanwhile,the phosphorylation of Akt、STAT3 was inhibited and the expression of Bcl-2 was down-regulated in SKOV3/DDP-shCTHRC1 cells (P<0.05).Conclusions:CTHRC1 may regulate Akt、STAT3/BcL-2 signaling to enhance the cisplatin-resistance in ovarian cancer cells.