白花蛇舌草水提物通过抑制MAPK通路致肺癌细胞的凋亡  

Hedyotis diffusa Willd Promotes the Apoptosis of Lung Cancer Cells by Inhibiting MAPK Pathway

作　　者：郭洪梅[1] 赵丹[1] 曹琳 夏辉[1] GUO Hongmei;ZHAO Dan;CAO Lin;XIA Hui(Department of Pharmacy,Xuzhou NO.1 People's Hospital,Xuzhou 221000)

机构地区：[1]徐州市第一人民医院药学部,徐州221000

出　　处：《药学与临床研究》2019年第1期5-9,共5页Pharmaceutical and Clinical Research

摘　　要：目的:研究白花蛇舌草(BHSSC)水提物对肺癌细胞增殖、凋亡的影响以及体内抑制肿瘤活性,进一步通过研究其对凋亡关键通路MAPK信号通路的影响,以阐明白花蛇舌草抗肺癌分子机制。方法:制备BHSSC水提取物,采用MTT法研究其对人肺癌细胞株A549和PC-9细胞体外增殖的抑制活性,并进一步构建人肺癌的裸鼠移植瘤模型,研究BHSSC水提物的体内抗肿瘤活性;通过Western blot技术研究BHSSC水提取物对MAPK通路中关键蛋白Erk、JNK、p38的表达水平和磷酸化水平的影响,进而阐明白花蛇舌草诱导肺癌细胞凋亡机制。结果 :BHSSC水提取物可以剂量依赖性地促进肺癌细胞的凋亡,从而抑制肺癌细胞的增殖。当剂量达到600μg·mL-1时,肺癌细胞抑制率达到95%(P<0.01)。荷瘤裸鼠模型结果显示,在给药21天后,给药组与肺癌模型组相比,肿瘤体积显著减小,平均抑瘤率达到70%(P<0.01)。Western blot结果提示,BHSSC水提物能够显著抑制MAPK通路中关键蛋白p38、Erk、JNK的磷酸化水平。结论:BHSSC水提物能够通过抑制肺癌细胞MAPK通路的活化,促进肺癌细胞凋亡,从而抑制肺癌的体内体外增殖。Objective:To study the effect of Hedyotis diffusa Willd on proliferation and apoptosis of lung cancer cells as well as to clarify its role in MAPK signaling pathway.Methods:The water extracts of Hedyotis diffusa Willd were prepared and their effects on human lung cancer cell line A549 and PC9 cell proliferation and apoptosis were observed.Furthermore,antitumor activity in vivo was studied by building the transplantation tumor model of lung cancer in nude mice.At last,the induced apoptosis mechanism of Hedyotis diffusa Willd water extract was illustrated by detecting the levels of Erk,Junk and p38 in the key MAPK pathway through Western blot technique.Results:The water extracts of Hedyotis diffusa Willd promoted the apoptosis and inhibited the proliferation of lung cancer cells.When the dose reached 600 mg·mL-1,95%of the cancer cells were killed.In addition,the growth of the transplanted tumor was significantly inhibited by the Hedyotis diffusa Willd.Compared with the model group,the tumor volume was significantly smaller after 21 days.Western blot results indicated that the water extracts of Hedyotis diffusa Willd mainly promoted the apoptosis of lung cancer cells by inhibiting the phosphorylation of key proteins p38,Erk and Junk in the MAPK pathway,thus inhibiting their proliferation.Conclusion:The aqueous extracts of Hedyotis diffusa Willd could inhibit the activation of MAPK pathway in lung cancer cells,promote the apoptosis of lung cancer cells,and inhibit the proliferation of lung cancer in vitro and in vivo.

关 键 词：白花蛇舌草 肺癌 细胞凋亡 MAPK 

分 类 号：R965.1[医药卫生—药理学]