PI-103对人卵巢癌细胞株SKOV3／DDP顺铂化疗效果的影响

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PI3 K/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。

Effect of PI-103 on DDP chemotherapy of human ovarian cancer cell line SKOV3/DDP

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 rpS 6 ,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 SKOV 3/DDP cells.PI-103 can effectively increase the chemotherapeutic effect of cisplatin on the cisplatin-resistance of SKOV3/DDP cells.