丙戊酸钠对肺腺癌细胞的增殖、迁移能力的影响  

Effect of valproate on proliferation and migration of lung adenocarcinoma cells

作　　者：代丽丽 束军[1] 朱宁 张梅[1] 沈继龙[2] Dai Lili;Shu Jun;Zhu Ning(Dept of Respiratory Medicine,The Fourth Affiliated Hospital of Anhui Medical University,Hefei 230032)

机构地区：[1]安徽医科大学第四附属医院呼吸内科,合肥230032 [2]安徽病原生物学省级实验室和人兽共患病安徽重点实验室,安徽医科大学基础医学院病原生物学教研室,合肥230032

出　　处：《安徽医科大学学报》2020年第5期702-706,共5页Acta Universitatis Medicinalis Anhui

基　　金：安徽省自然科学基金(编号:1308085MH141);安徽高校省级自然科学研究项目(编号:KJ2018A0204)。

摘　　要：目的探讨不同浓度丙戊酸钠(VPA)对肺腺癌PC9细胞增殖、迁移能力的影响及其可能的机制。方法体外培养PC9细胞,实验分为对照组(无VPA处理组)和实验组(VPA处理组,浓度分别为2、4、8、16 mmol/L),检测不同浓度VPA在不同作用时间条件下对PC9细胞增殖、迁移能力的影响分别使用CCK-8、划痕实验;检测不同浓度VPA对乳酸脱氢酶(LDH)活性、乳酸(LD)生成量的影响分别使用(LDH)活性检测试剂盒、LD定量试剂盒,检测VPA干预PC9细胞后上清液及细胞内的E-钙黏蛋白(E-cad)及波形蛋白(VIM)的表达水平用ELISA法。结果CCK-8结果表明,VPA可以抑制PC9细胞的增殖,并且呈现出浓度依赖性和时间依赖性(P<0.05)。划痕实验结果表明,实验组细胞迁移距离小于对照组(P<0.05),划痕宽度比对照组窄。VPA浓度越高,迁移距离越短(P<0.05),划痕宽度越窄。LDH活性和LD检测结果表明,实验组LDH活性和LD生成量较对照组显著降低(P<0.05),随着VPA浓度的增加,LDH活性和LD生成量逐渐降低(P<0.05)。ELISA结果显示,实验组细胞内外E-cad蛋白浓度与对照组相比均显著增高,并且随着VPA浓度增加,E-cad浓度逐渐增高(P<0.05);实验组细胞内外VIM蛋白浓度与对照组相比均显著降低,并且随着VPA浓度增加,VIM蛋白浓度逐渐降低(P<0.05)。结论VPA在体外能够抑制PC9细胞的增殖、迁移,且有可能是通过抑制有氧糖酵解和上皮间质转化途径。Objective To research the effects of sodium valproate(VPA)on proliferation,migration of human lung adenocarcinoma PC9 cells in different concentrations and its possible mechanism.Methods PC9 cells were divided into control group(0 mmol/L VPA)and experimental groups(2,4,8 and 16mmol/L VPA),and they were cultured in vitro.CCk-8 and scratch test were used to detect the effects of VPA of different concentrations on the proliferation and migration ability of PC9 cells under different time conditions.The effects of VPA on lactate dehydrogenase activity and lactic acid production in different concentrations were detected by lactate dehydrogenase activity assay kit and lactate quantitative assay kit respectively.ELISA was used to detect the expression levels of E-caducin(E-cad)and vimentin(VIM)in cell culture supernatant and in cells.Results CCK-8 result revealed that VPA had a concentration-dependent and time-dependent cell proliferation inhibition effect on PC9 cells(P<0.05).The scratch test result indicated that the migration distances of the experimental groups were smaller than that of the control group(P<0.05),and the migration distance gradually decreased when VPA concentration increased(P<0.05).LDH activity and LD test results indicated that the activity of LDH and LD production of the experimental groups were significantly lower than that of the control group(P<0.05).LDH activity and LD production gradually decreased when VPA concentration increased(P<0.05).ELISA results indicated that the cell culture supernatant and cells in the experimental groups had more E-cad protein than the control group,and the concentration of E-cad increased gradually when VPA concentration increased(P<0.05).The cell culture supernatant and cells in the experimental group had less VIM protein than the control group,and VIM protein concentration gradually decreased when VPA concentration increased(P<0.05).Conclusion The proliferation and migration of PC9 cells in vitro can be restrained by VPA,possibly by restraining aerobic glycolysis

关 键 词：丙戊酸钠 肺腺癌 增殖 迁移 

分 类 号：R734.2[医药卫生—肿瘤]