蛋白激酶C抑制剂对宫颈癌细胞化疗药物耐药的影响

目的观察蛋白激酶C抑制剂星形孢菌素对经紫杉醇处理的宫颈癌细胞增殖、凋亡及蛋白激酶C、P-糖蛋白（P-gp）表达的变化,探讨蛋白激酶C抑制剂对宫颈癌细胞紫杉醇耐药的影响。方法培养人宫颈癌Hela细胞,设立星形孢菌素组、紫杉醇组、联合组及对照组。星形孢菌素组加入星形孢菌素0.6μmol/L;紫杉醇组加入紫杉醇0.1μmol/L;联合组先加入星形孢菌素0.6μmol/L,随后加入紫杉醇0.1μmol/L;对照组不加入星形孢菌素及紫杉醇。四组细胞干预后继续培养48 h,采用MTT法检测细胞增殖能力,流式细胞术检测细胞凋亡率,Western blot法检测蛋白激酶C及P-gp蛋白表达。结果星形孢菌素组、紫杉醇组及联合组增殖抑制率分别为38.11%±0.70%、49.96%±1.60%及60.31%±1.80%,联合组增殖抑制率高于星形孢菌素组及紫杉醇组（P均〈0.05）,星形孢菌素组增殖抑制率低于紫杉醇组（P〈0.05）。对照组、星形孢菌素组、紫杉醇组及联合组细胞凋亡率分别为7.13%±0.56%、17.73%±0.59%、36.51%±0.34%、56.72%±0.68%,星形孢菌素组、紫杉醇组及联合组细胞凋亡率均高于对照组（P均〈0.05）,联合组细胞凋亡率高于其他三组（P均〈0.05）。星形孢菌素组、联合组蛋白激酶C及P-gp蛋白表达均低于对照组（P均〈0.05）,联合组蛋白激酶C及P-gp蛋白表达均低于星形孢菌素组、紫杉醇组（P均〈0.01）。结论星形孢菌素可抑制经紫杉醇处理后的宫颈癌细胞的增殖、促进其凋亡,改善宫颈癌细胞对紫杉醇的耐药性。星形孢菌素可能通过减少P-gp蛋白表达改善宫颈癌细胞对紫杉醇的耐药性。

Effect of protein kinase C inhibitors on the chemotherapeutic drug resistance of cervical carcinoma cell

Objective To study the effect of protein kinase C inhibitors combined with paclitaxel on proliferation,apoptosis,kinase C and P-glycoprotein（ P-gp） expression of cervical cancer cell,in order to explore the effect of protein kinase C inhibitor on the drug resistance of cervical cancer. Methods Cervical cancer Hela cells were cultured and divided into 4 groups,which were staurosporin group,paclitaxel group,combination group and control group. Staurosporin group were cultured with 0. 6μmol /L staurosporin. Paclitaxel group were cultured with 0. 1 μmol /L paclitaxel. Combination group were cultured with 0. 6μmol /L staurosporin and 0. 1 μmol /L paclitaxel. Control group did not culture with staurosporin and paclitaxel. At 48 hours later,the cell proliferation of each group was performed by MTT method; the cell apoptosis were detected by flow cytometry（ FCM）method; the expression of protein kinase C and P-gp were detected by western-blot method. Results The proliferation of staurosporin group,paclitaxel group,combination group was 38. 11% ± 0. 70%,49. 96% ± 1. 60% and 60. 31% ± 1. 80%,respectively. The proliferation of combination group was higher than that of staurosporin group and paclitaxel group（ P〈0. 05）. The proliferation of staurosporin group was lower than that of paclitaxel group（ P〈0. 05）. The cell apoptosis of control group,staurosporin group,paclitaxel group and combination group was 7. 13% ± 0. 56%,17. 73% ± 0. 59%,36. 51% ± 0. 34% and 56. 72% ±0. 68%,respectively. The cell apoptosis of staurosporin group,paclitaxel group and combination group was higher than that of control group（ P〈0. 05）. The expression of protein kinase C and P-gp in staurosporin group and combination group were lower than those of control group（ P〈0. 05）. The expression of protein kinase C and P-gp in combination group were lower than those of staurosporin group and paclitaxel group（ P〈0. 05）. Conclusions The protein kinase C inhibits staurosporin can inhibit the proliferation of cerv