【摘要】 目的探讨mTOR信号通路的功能状态与肺癌对雷帕霉素敏感度的关系。方法 Westernblot检测mTOR信号通路中AKT、S6K1、eIF4E、4E-BP1、P-S6K1蛋白在4种人肺癌细胞株的表达;MTT法检测雷帕霉素对肺癌细胞增殖的抑制情况,将肺癌细胞分为雷帕霉素敏感组和不敏感组,找出与敏感度相关的差异蛋白,用En Vision法检测患者肺癌组织中差异蛋白的表达。结果 AKT、S6K1、eIF4E、4E-BP1蛋白在4种肺癌细胞株中均有表达。而P-S6K1在不敏感株中未检测到,在敏感株中呈高表达,为雷帕霉素差异蛋白。P-S6K1在正常肺组织中的阳性表达率为15%(3/20例),在肺癌组织中的阳性表达率为62%(62/100例),其中在小细胞肺癌组织中的阳性表达率(81.0%,17/21例)高于非小细胞肺癌组织(59%,45/79例)。结论在mTOR信号通路相关蛋白中,仅P-S6K1在一定程度上可预测肺癌细胞株对雷帕霉素的敏感度,为一种mTOR靶向抑制剂———雷帕霉素治疗肺癌的差异蛋白。P-S6K1在小细胞肺癌中表达较非小细胞肺癌高,提示在P-S6K1表达率高的小细胞未分化肺癌中应用mTOR靶向抑制剂———雷帕霉素的疗效可能更佳。更多还原

【Abstract】 Objective To investigate the relation between the function state of mTOR signal pathway and rapamycin sensitivity to lung cancer.Methods mTOR signaling pathway protein in 4 lung cancer cell lines(HLAMP,H1299,A549 and PAa) were detected by Western Blot.MTT method was used to determine the inhibitory effect of rapamycin on human lung cancer cell.Lung cancer cell lines were divided into rapamycin sensitive group and non-sensitive group.En Vision method was used to detecte the expression of rapamycin differential protein in 100 lung cancer and 20 lung nonmalignant disease normal lung tissues.Result AKT,S6K1,4E-BP1,eIF4E were expressed in all human lung cancer cell lines.P-S6K1 was high-level expression in sensitive cell lines,no detection in non-sensitive cell line,and it was arapamycin differential protein.P-S6K1 positive-expression rate was 15%(3/20)in normal lung tissues,and 62%(62/100) in lung cancer,respectively.P-S6K1 positive-expression rate in small cell lung cancer(81%,17/21)was higher than that in non-small cell lung cancer(59%,45/79).Conclusion The expression of P-S6K1 in human lung cancer cell lines may reflect rapamycin sensitivity to cancer cell to a extent.But other mTOR signaling pathway protein(AKT,S6K1,eIF4E,4E-BP1)can not reflect rapamycin sensitivity to lung cancer cell.P-S6K1 isarapamycin differential protein.The expression of P-S6K1 in small cell lung cancer is much higher than that in non-samll cell lung cancer.The results suggest the better clinical effect of mTOR inhibitor-rapamycin in small cell lung cancer.更多还原