PI-103对人卵巢癌细胞株SKOV3/DDP顺铂化疗效果的影响-东南大学学报医学版

PI-103对人卵巢癌细胞株SKOV3/DDP顺铂化疗效果的影响

单位：1. 东南大学医学院江苏南京 210009;
2. 东南大学附属中大医院妇产科, 江苏南京 210009

关键词：PI-103 人卵巢浆液性乳头状囊腺癌顺铂耐药细胞株磷脂酰肌醇3激酶/蛋白激酶B/哺乳动物雷帕霉素靶体蛋白信号通路顺铂

分类号：R711.75;R339.22

出版年·卷·期（页码）：2013·32·第五期（574-579）

摘要：

目的:探讨磷脂酰肌醇3-激酶(PI3K)/哺乳动物雷帕霉素靶蛋白(mTOR)双抑制剂PI-103对卵巢癌耐顺铂株SKOV3/DDP顺铂化疗效果的影响。方法:将PI-103、顺铂及两者联合分别作用于SKOV3/DDP细胞,采用CCK-8法检测细胞生长情况,流式细胞技术检测药物单独或联合作用对细胞凋亡的影响;应用Western blot检测蛋白激酶B(Akt)、磷酸化Akt(p-Akt)、核糖体蛋白(rpS6)、磷酸化rpS6(p-rpS6)以及凋亡相关蛋白Bcl-2与Bax蛋白表达变化。结果:PI-103能够抑制SKOV3/DDP细胞增殖,且呈浓度、时间依赖性;联合用药可以明显增加对细胞生长抑制和凋亡作用。PI-103能下调Akt和rpS6的磷酸化水平,促DDP上调Bax和下调Bcl-2的表达。结论:PI-103抑制PI3K/Akt/mTOR信号传导通路,促DDP上调促凋亡蛋白及下调抗凋亡蛋白的表达,从而抑制癌细胞生长,诱导其凋亡,增加卵巢癌耐顺铂株SKOV3/DDP细胞对DDP的化疗效果。

Objective:To explore the effect of PI-103, a phosphatidylinositol 3'-kinase(PI3K)-mammalian target of rapamycin(mTOR)inhibitor, in DDP chemotherapy on cisplatin-resistance of human ovarian cancer cell line SKOV3/DDP.Methods:The SKOV3/DDP cells proliferation treated with PI-103 and DDP alone or in combin-ation was evaluated by CCK-8 assay. Flow cytometry was used to study cell apoptosis upon drug treatment.Western blot was used to detect the changes of protein kinase B(Akt), phosphorylated Akt protein, S6 ribosomal protein(rpS6), phosphorylated rpS6 protein, Bcl-2 and Bax protein upon drug treatment. Results: PI-103 could effecti-vely inhibit the multiplication of SKOV3/DDP cells.The inhibition effect showed a dose-dependent and time-depe-ndent fashion.The inhibition ratio of SKOV3/DDP cells proliferation and the apoptotic index were increased more obviously by cisplatin in combination with PI-103 than both individually.PI-103 specifically abrogated the phosp-horylation of Akt and rpS6,and enhanced up-regulation of Bax and down-regulation of Bcl-2 with DDP treatment.Conclusions:Inhibition of the PI3K/Akt/mTOR signaling pathway by PI-103,can enhance up-regulation of pro-apoptotic protein and simultaneously down-regulation of anti-apoptosis protein with DDP treatment,which finally induced cell growth inhibition and cell apoptosis in SKOV3/DDP cells.PI-103 can effectively increase the chemotherapeutic effect of cisplatin on the cisplatin-resistance of SKOV3/DDP cells.

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