化疗联合二甲双胍治疗前后非小细胞肺癌患者外周血中IGF-1和mTOR表达变化及其疗效分析

doi:10.13481/j.1671-587x.20200119

摘要/Abstract

摘要： 目的：观察化疗联合二甲双胍治疗后非小细胞肺癌（NSCLC）患者外周血中胰岛素样生长因子1（IGF-1）和雷帕霉素靶蛋白（mTOR）的表达变化及临床疗效，并阐明其作用机制。方法：60例NSCLC患者根据采用的治疗方法不同分为化疗组（腺癌和鳞癌各15例，采用单纯化疗）和联合组（腺癌和鳞癌各15例，采用化疗联合二甲双胍治疗）。采用ELISA法和实时荧光定量PCR（QT-PCR）法分别检测2组患者外周血中IGF-1和mTOR水平及mRNA表达水平，应用Pearson单因素分析和多因素Logistic回归分析法分析晚期NSCLC患者治疗的影响因素，综合评估疗效。结果：与化疗组比较，联合组患者治疗后与治疗前外周血中IGF-1和mTOR水平及mRNA表达水平差值均降低（t=-3.207，P=0.003；t=2.414，P=0.019；t=-3.635，P=0.001；t=-3.737，P=0.001）。在腺癌中，与化疗组比较，联合组患者治疗后与治疗前外周血中IGF-1和mTOR水平及mRNA表达水平差值均降低（t=5.270，P<0.01；t=2.816，P=0.009；t=-2.621，P=0.019；t=4.039，P<0.01）；在鳞癌中，与化疗组比较，联合组患者治疗后与治疗前外周血中IGF-1和mTOR水平及mRNA表达水平差值均降低（t=4.164，P<0.01；t=2.670，P=0.012；t=-2.621，P<0.01；t=3.502，P=0.002）。从疾病控制率的层面，联合组患者总有效率（80.0%）明显高于化疗组（53.3%）（P<0.05）。单因素分析，患者性别、吸烟、肿瘤分期和淋巴结转移与2组患者疗效有关（均P<0.05）；美国东部肿瘤协作组（ECOG）评分和肿瘤分化程度与化疗组患者疗效有关（均P<0.05），胸腔积液与联合组患者疗效有关（P<0.05）。多因素分析，吸烟和肿瘤分期是2组患者的独立危险因素（均P<0.05），吸烟和淋巴结转移是化疗组患者的独立危险因素（均P<0.05），吸烟、分化程度和胸腔积液是联合组患者的独立危险因素（均P<0.05）。与化疗组比较，联合组患者骨髓抑制、胃肠道反应、肾毒性和肝脏损害的发生率差异均无统计学意义（P>0.05）。结论：化疗联合二甲双胍治疗NSCLC患者的效果较好，且能降低其不良反应，其机制可能与降低患者外周血中IGF-1和mTOR水平有关。

关键词: 二甲双胍, 化学疗法, 癌,非小细胞肺, 胰岛素样生长因子1, 雷帕霉素靶蛋白

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

中图分类号:

R734.2

李瑞阳, 林芷伊, 李晶, 费晶, 徐丹, 巩平. 化疗联合二甲双胍治疗前后非小细胞肺癌患者外周血中IGF-1和mTOR表达变化及其疗效分析[J]. 吉林大学学报(医学版), 2020, 46(01): 108-115.

LI Ruiyang, LIN Zhiyi, LI Jing, FEI Jing, XU Dan, GONG Ping. Changes of IGF-1 and mTOR expressions in peripheral blood of patients with non-small cell lung cancer before and after chemotherapy combined with metformin and analysis on their therapeutic effects[J]. Journal of Jilin University(Medicine Edition), 2020, 46(01): 108-115.

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