Abstract: Objective: To observe the expression changes of insulin-like growth factor 1(IGF-1)and mammalian target of rapamycin(mTOR)in the peripheral blood of patients with advanced non-small cell lung cancer (NSCLC) treated with chemotherapy combined with metformin, and to elucidate its mechanism. Methods: Sixty patients with NSCLC were divided into chemotherapy group (15 cases of adenocarcinoma and squamous cell carcinoma, treated with chemotherapy alone) and combination group (15 cases of adenocarcinoma and squamous cell carcinoma, treated with chemotherapy combined with metformin). The expression levels of IGF-1 and mTOR protein and mRNA in peripheral blood of the patients in two groups were detected by ELISA and quantitative real-time PCR(QT-PCR) method. Pearson univariate analysis and multivariate logistic regression analysis were used to analyze the influencing factors of the treatment of patients with advanced NSCLC;the curative effect was comprehensively evaluated. Results: Compared with chemotherapy group, the differences of the levels of IGF-1 and mTOR and the mRNA expression levels of IGF-1 and mTOR of the patients in combination group before and after treatment were decreased (t=-3.207, P=0.003; t=2.414, P=0.019; t=-3.635, P=0.001; t=-3.737, P=0.001). In adenocarcinoma, compared with chemotherapy group, the differences the levels of IGF-1 and mTOR and the mRNA expression levels of IGF-1 and mTOR of the patients in combination group before and after treatment were decreased (t=5.270, P<0.01; t=2.816, P=0.009; t=-2.621, P=0.019; t=4.039, P<0.01); in squamous cell carcinoma, compared with chemotherapy group, the differences of the levels of IGF-1 and mTOR and the mRNA expression levels of IGF-1 and mTOR in peripheral blood of the patients in combination group before and after treatment were reduced (t=4.164, P<0.01; t=2.670, P=0.012; t=3.072, P=0.008; t=3.502, P=0.002). From the level of disease control rate, the total effective rate of the patients in combination group (80.0%) was significantly higher than that in chemotherapy group (53.3%) (P<0.05).The univariate analysis results showed that gender, smoking, tumor stage, and lymph node metastasis were related to the therapeutic effects of the patients in two groups (P<0.05);the ECOG score and tumor differentiation degree were related to the therapeutic effect of the patients in chemotherapy group (P<0.05),and pleural effusion was related with the therapeutic effect of the patients in combination group (P<0.05). The results of multivariate analysis showed that smoking and tumor stage were the independent risk factors of the patients in two groups (P<0.05),and smoking and lymph node metastasis were the independent risk factors of the patiens in chemotherapy group(P<0.05); smoking, differentiation, and pleural effusion were the independent risk factors of the patients in combination group (P<0.05).Compared with chemotherapy group, the incidences of bone marrow suppression, gastrointestinal reactions, nephrotoxicity, and liver damage of the patients in combination group had no significant differences(P>0.05). Conclusion: Chemotherapy combined with metformin is more effective in the treatment of the patients with NSCLC and can reduce its adverse reactions, its mechanism may be related to the reduction of IGF-1 and mTOR levels in the peripheral blood of the patients.

Key words: metformin, chemotherapy, cancer, non-small cell lung, insulin-like growth factor 1, mammalian target of rapamycin