| 抑制PI3K/PKB信号通路提高胃癌细胞化疗敏感性的研究 |
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| 引用本文： | 谢霞,高青,王艳丽,田翀.抑制PI3K/PKB信号通路提高胃癌细胞化疗敏感性的研究[J].中国药理学通报,2008,24(12). |
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| 作者姓名： | 谢霞 高青 王艳丽 田翀 |
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| 作者单位： | 重庆医科大学附属第一医院消化内科,重庆,400016 |
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| 摘 要： | 目的探讨磷脂酰肌醇3激酶(phosphatidylinositol 3-kinase,PI3K)抑制剂LY294002提高胃癌耐药细胞SGC7901/VCR和亲代细胞SGC7901对化疗药物敏感性的作用及其机制。方法MTT法分别检测胃癌细胞SGC7901和SGC7901/VCR对化疗药长春新碱(VCR)的敏感性;RT-PCR法和免疫细胞化学法检测LY294002处理前后多药耐药蛋白1(multidrug resistance protein-1,MDR1)和X染色体连锁的凋亡抑制蛋白(X-linked inhibitor of apoptosis,XIAP)基因和蛋白水平;Westernblot法检测LY294002处理前后细胞PKB总蛋白水平和磷酸化水平;并用流式细胞仪检测细胞的凋亡率。结果2×10-5mol·L-1 LY294002能明显增加SGC7901和SGC7901/VCR细胞对VCR的敏感性(P<0.01),其IC50分别由(0.20±0.03)和(8.09±0.60)mg·L-1降至(0.05±0.006)和(1.70±0.20)mg·L-1;降低细胞MDR1和XIAP的基因和蛋白水平;降低磷酸化PKB水平,而对其总蛋白水平无影响;LY294002联合VCR用药后细胞凋亡率明显高于单独VCR处理(P<0.01)。结论LY294002通过降低耐药基因MDR1和抗凋亡基因XIAP的表达,提高耐药和非耐药胃癌细胞对化疗药物的敏感性,此过程与抑制PI3K/PKB通路密切相关。
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| 关 键 词： | LY294002 SGC7901细胞 SGC7901/VCR耐药细胞 细胞凋亡 |
Inhibition of PI3K/PKB signal pathway improves chemotherapeutic effect on gastric carcinoma cell lines |
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| XIE Xia,GAO Qing,WANG Yan-li,TIAN Chun.Inhibition of PI3K/PKB signal pathway improves chemotherapeutic effect on gastric carcinoma cell lines[J].Chinese Pharmacological Bulletin,2008,24(12). |
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| Authors: | XIE Xia GAO Qing WANG Yan-li TIAN Chun |
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| Affiliation: | XIE Xia,GAO Qing,WANG Yan-li,TIAN Chun(Dept of Gastroenterology,the First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China) |
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| Abstract: | Aim To observe whether the inhibition of PI3K/PKB signal pathway by LY294002PI3K pathway inhibitor] could improve the sensitivities of human gastric carcinoma cell line SGC7901 and SGC7901/VCR to anti-cancer drugs.Methods The sensitivities of SGC7901 and SGC7901/VCR to chemotherapeutic drug VCR were detected by MTT.The MDR1 and XIAP mRNA expression levels were evaluated by semi-quantitative RT-PCR,and their protein levels were detected by immunocytochemistry.The PKB and phospho-PKB protein levels were dete... |
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| Keywords: | LY294002 |
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