基于PKCα-ERK1/2信号通路研究竹节参皂苷抑制肺癌的作用机理

目的:研究竹节参皂苷(Saponins from Panax Japonicus,SPJ)对Lewis肺癌移植瘤小鼠的影响以及对PKCα-ERK1/2信号通路的调控作用。方法:应用Lewis肺癌小鼠荷瘤模型,灌胃给予竹节参皂苷15 mg/kg·d,30 mg/kg·d和60 mg/kg·d,连续20 d,比较各组小鼠肿瘤体积,计算肿瘤生长曲线,ELISA法测定血清中VEGF和MMP 9水平,Western blot测定PKCα、P-PKCα、ERK1/2、P-ER K1/2蛋白表达情况。结果:与荷瘤对照组比较,SPJ给药组肿瘤体积增加缓慢,具有统计学差异(P<0.01);同时SPJ可显著降低血清中VEGF和MMP 9水平(P<0.01),降低PKCα和ERK1/2磷酸化水平(P<0.01);进一步采用静脉注射PKCα激动剂PMA 25μg/kg·d,连续10 d进行验证发现其可减弱SPJ对ERK1/2磷酸和肿瘤生长的抑制作用(P<0.01)。结论:SPJ对Lewis肺癌移植瘤小鼠模型肿瘤生长和转移具有抑制作用,其作用机制可能是抑制了PKCα-ERK1/2信号通路。

Saponins from Panax Japonicus Inhibited Lung Cancer Through PKCα-ERK1/2 Signaling Pathway

Objective:To study the effect of saponins from Panax Japonicus(SPJ)on Lewis lung cancer transplanted tumor mice and the regulation of PKCα-ERK1/2 signaling pathway.Methods:The model of mice transplanted Lewis lung cell was used and then treated by saponins from Panax Japonicus 15 mg/kg·d,30 mg/kg·d and 60 mg/kg·d for 20 days.The tumor volume in each mice was collected and the tumor growth curve was calculated.Levels of VEGF and MMP9 in serum were determined by ELISA method.The expression of PKCα,P-PKCαand ERK1/2,P-ERK1/2 protein was determined by Western blot.Results:Compared with the tumor-bearing control group,the tumor volume increased slowly in the saponins-treated group,and had a significant difference(P<0.01).At the same time,SPJ significantly inhibited VEGF and MMP9 levels in serum(P<0.01),and the phosphorylation of PKCαand ERK1/2(P<0.01).Further verification with PKCαagonist PMA 25μg/kg·d showed that PMA abolished the inhibitory effect of SPJ on ERK1/2 phosphorylation and tumor volume(P<0.01).Conclusion:SPJ inhibited the growth and metastasis of tumor in Lewis lung cancer transplanted mice,which mechanism might be related to the regulation of PKCα-ERK1/2 signaling pathway.