色素上皮衍生因子对高糖环境下肺鳞癌细胞增殖、凋亡及侵袭的影响

Effects of PEDF on proliferation, apoptosis and invasion of squamous lung carcinoma cells in high-glucose environment

目的研究色素上皮衍生因子(PEDF)对高糖环境下肺鳞癌细胞株增殖、凋亡、侵袭的影响,探索PEDF对肺癌合并糖尿病的疾病发展、预后及治疗的意义。方法培养肺鳞癌细胞株SK-MES-1,分为阴性对照组、高糖组及PEDF干预高糖1、2、3组,倒置显微镜观察各组细胞形态改变;MTT比色法分析各组细胞增殖抑制率;流式细胞术检测各组细胞周期和凋亡率;Transwell细胞侵袭实验检测各组细胞穿透数;ELISA法检测各组细胞培养基上清液中VEGF的表达。结果①高糖组较阴性对照组细胞增殖抑制率降低、凋亡率降低、阻滞于G0/G1期的百分比相对减少、细胞穿透数增加、VEGF浓度增高(P<0.05);②随着PEDF干预浓度的增高,各组细胞的增殖抑制率和凋亡率、G0/G1期的百分比增加,细胞穿透数减少,VEGF浓度降低,各组差异有统计学意义(P<0.05);结论①高糖环境促进肺鳞癌发展。②PEDF抑制高糖环境下肺鳞癌细胞的增殖,促进早期凋亡,减弱侵袭力,并呈浓度依赖;预测PEDF将成为肺癌合并糖尿病的靶向治疗药物。

Objective To study the effects of pigment epithelial-derived factor(PEDF)on the proliferation,apoptosis and invasion of squamous lung carcinoma cells in high-glucose environment so as to explore the significance of PEDF in the development,prognosis and treatment of lung cancer associated with diabetes.Methods SK-MES-1 lung squamous carcinoma cells were cultured and divided into negative control group;high-glucose group;and PEDF+high glucose groups 1,2 and 3.The cell morphological changes were observed under the inverted microscope.Then proliferation inhibition rates of SK-MES-1 cells in all the groups were observed by MTT assay.The cell cycle and cell apoptosis rates were detected by flow cytometry.The number of penetration cells was determined by cell invasion experiment.Expression of VEGF in culture supernatant in each group was detected by ELISA.Results①Compared with that in the negative control group,the proliferation inhibition rate and apoptosis rate in high-glucose group were low,the percentage of cells blocked in G0/G1 phase was decreased,the number of penetration cells was increased and the concentration of VEGF was increased(P<0.05).②With the increase of PEDF intervention concentration,the proliferation inhibition rate and apoptosis rate in each group increased,the percentage of G0/G1 phase increased,the number of penetration cells decreased,and the concentration of VEGF decreased(P<0.05).Conclusion①The development of squamous cell carcinoma of the lung is promoted in high glucose.②PEDF can inhibit the proliferation of lung squamous cell carcinoma cells in high-glucose environment,promote early apoptosis and reduce the invasiveness in the concentration-dependent manner.PEDF is predicted to be a target therapeutic drug for lung cancer complicated with diabetes mellitus.