Background: Previous studies have reported that Met might be related to gefitinib resistance in non-small cell lung cancer (NSCLC). The present study aims to explore the mechanism of hepatocyte growth factor (HGF)-induced gefitinib resistance in different gene types of sensitive NSCLC in vitro.
Methods: The PC-9 and H292 cell lines were chosen and induced by HGF. The cell survival was measured using MTT assay, the cell cycle distribution was measured using PI assay, and cell apoptosis with an Annexin V-PE assay, respectively. The c-Met and p-Met protein expression was determined via Western blot analysis.
Results: Gefitinib inhibited the growth of PC-9 and H292 cells in a dose-dependent manner. The concentration-survival curves of both cell lines shifted to the right when induced with HGF. HGF did not affect PC-9 and H292 cell proliferation. The cell also had a higher cell survival rate when treated with HGF and gefitinib compared with that under gefitinib alone (P<0.05). The apoptotic rate and cell cycle progression showed no significant difference between the HG and G group (P>0.05). HGF stimulated Met phosphorylation in the PC-9 and H292 cells. Gefitinib inhibited the HGF-induced Met phosphorylation in PC-9 cells, but not in H292 cells.
Conclusions: HGF induces gefitinib resistance in PC-9 and H292 cells. HGF-induced Met phosphorylation may be an important mechanism of gefitinib resistance in sensitive NSCLC.
背景与目的: 肝细胞生长因子（hepatocyte growth factor, HGF）受体（c-Met）可能与非小细胞肺癌（non-small cell lung cancer, NSCLC）对吉非替尼耐药有关。本研究旨在探讨HGF诱导不同基因型NSCLC对吉非替尼耐药及耐药机制。
方法: 选择NSCLC细胞EGFR突变型PC-9和EGFR野生型H292，用HGF诱导这两株细胞，通过MTT法检测细胞增殖，PI法检测细胞周期，Annexin V-PE法检测细胞凋亡，应用免疫印迹（Western blot）技术检测细胞中c-Met、p-Met的表达。
结果: 吉非替尼对PC-9和H292的生长抑制作用呈浓度依赖性，HGF诱导后吉非替尼抑制两种细胞的生长曲线往右移。PC-9和H292的HGF和吉非替尼处理组（HG）比吉非替尼处理组（G）均有更高的存活率（P < 0.05），HG组与G组两组间细胞凋亡及细胞周期无统计学差异（P > 0.05）。HGF明显增加PC-9和H292中p-Met的表达。吉非替尼能明显抑制HGF诱导PC-9增加表达的p-Met，但不能抑制HGF诱导H292增加表达的p-Met。
结论: HGF可诱导敏感肺癌细胞PC-9和H292对吉非替尼耐药，HGF刺激c-Met磷酸化可能是敏感肺癌细胞对吉非替尼耐药的重要机制。