Study on effect and mechanisms of IL-6 induced Gefitinib resistance in non-small cell lung cancer / 重庆医学

ABSTRACT

Objective To evaluate the effect and mechanism of IL‐6 induced Gefitinib resistance in non small cell lung cancer (NSCLC) .Methods The sensitivity of cells to Gefitinib ,the invasion ability of cells and the expression of phosphorylated p‐mTOR was assessed by MTT assay ,Transwell assay and Western blot ,respectively .PC‐9psb388 stable over expressing human recombi‐nant IL‐6(hrIL‐6) cell line was established by transfecting PC‐9 cells with a lentivirus psb388 expressing IL‐6 and stable transfecta‐nts over‐expressing IL‐6 in human lung cancer cell line PC‐9 .The sensitivity of cells to Gefitinib ,the invasion ability ,expression of p‐mTOR were then detected .PC‐9/PC‐9psb388 xenografts were established and the expression of p‐mTOR and IL‐6 in tumor sec‐tions were then detected .Results The sensitivity of PC‐9 cells to Gefitinib was reduced by IL‐6 ,the invasion ability of PC‐9 cells and the expression of p‐mTOR was significantly increased with IL‐6 treatment .The sensitivity of PC‐9 cells to Gefitinib was promi‐nent higher in PC‐9psb388 cells ,while the invasion ability of PC‐9psb388 cells and the expression of p‐mTOR was higher than PC‐9 cells .The sensitivity to Gefitinib was improved and expression of p‐mTOR reduced in rapamycin‐treated PC‐9psb388 cells and IL‐6 stimulated PC‐9 cells .Tumor volume of PC‐9psb388 xenografts was significantly higher than that of PC‐9 cells .The expression of p‐mTOR and IL‐6 in tumor sections of PC‐9psb388 group were higher than that of PC‐9 group .Conclusion IL‐6 could elevate the expression of p‐mTOR to induce Gefitinib resistance in non small cell lung cancer (NSCLC) .