摘要
目的探讨南方红豆杉水提物通过抑制Ras/MAPK信号通路相关靶点蛋白表达,调控裸鼠HER2阳性胃癌移植瘤生长及其机制。方法建立荷瘤裸鼠模型,将80只BALB/c裸鼠接种人表皮生长因子-2(HER2)阳性胃癌NCI-N87细胞株,并随机分组给药及取瘤,采用Western Blot检测HER2、KRAS蛋白表达,RT-PCR定量检测HER2、KRAS m RNA表达水平。结果 1Western blot检测HER2、KRAS蛋白:与空白组比较,各给药组HER2、KRAS蛋白表达不同程度下调[HER2:(1.238±0.123、1.180±0.152、1.159±0.087、0.876±0.098、0.651±0.108、0.554±0.110)比(1.482±0.101),P<0.05或P<0.01;KRAS:(0.768±0.040、0.680±0.019、0.821±0.170、0.716±0.023、0.630±0.049、0.739±0.044)比(1.015±0.033),P均<0.05];与赫赛汀组比较,中剂量联合组KRAS蛋白表达显著下调(0.630±0.049比0.759±0.029,P<0.05);2RT-PCR检测HER2、KRAS m RNA表达:与空白组比较,各给药组HER2、KRAS m RNA表达不同程度下调[HER2 m RNA:(0.916±0.026、0.783±0.061、0.846±0.021、0.741±0.079、0.660±0.079、0.673±0.045)比(1.000±0.193),P均<0.05;KRAS m RNA:(0.643±0.065、0.551±0.173、0.572±0.267、0.329±0.250、0.036±0.007、0.351±0.257)比(1.001±0.132),P<0.05或P<0.01];与赫赛汀组比较,中剂量联合组KRAS m RNA表达显著下调(0.036±0.007比0.362±0.162,P<0.01)。结论南方红豆杉水提物可通过Ras/MAPK信号通路部分下调HER2、KRAS蛋白及其m RNA表达水平,联合赫赛汀可增强其抑制作用。
Objective To investigate the effect of taxus chinensis water extract on human epidermal growth receptor 2(HER2)-positive gastric cancer via regulating Ras/MAPK pathway related proteins.Methods Nude mouse model bearing HER2-positive gastric cancer was established by inoculating NCI-N87 tumor strain.Eighty BALB/c mice were randomized into high-,middle-,low-dose taxus chinensis groups,high-,middle-,low-dose taxus chinensis+herceptin groups,and herceptin group and given the corresponding drugs.Mice were killed by cervical dislocation to obtain tumor tissue for inspection.The protein expression of HER2 and KRAS were detected with Western Blot and m RNA contents of the genes were determined by RT-PCR assay.Results Compared with blank group,the expression of HER2 and KRAS proteins were decreased in all drug groups(HER2:1.238±0.123,1.180±0.152,1.159 ±0.087,0.876 ±0.098,0.651 ±0.108,0.554 ±0.110 vs 1.482 ±0.101,P〈0.05 or P〈0.01;KRAS:0.768 ±0.040,0.680±0.019,0.821 ±0.170,0.716±0.023,0.630±0.049,0.739±0.044 vs 1.015±0.033,all P〈0.05).Compared with that in herceptin group,KRAS protein in middle-dose taxus chinensis+herceptin group was significantly de-creased(0.630±0.049 vs 0.759±0.029,P〈0.05).Compared with blank group,the expression of HER2 and KRAS m RNA were decreased in all drug groups(HER2 m RNA:0.916±0.026,0.783 ±0.061,0.846 ±0.021,0.741 ±0.079,0.660 ±0.079,0.673 ±0.045 vs 1.000 ±0.193,all P〈0.05;KRAS m RNA:0.643 ±0.065,0.551 ±0.173,0.572 ±0.267,0.329±0.250,0.036±0.007,0.351±0.257 vs 1.001±0.132,P〈0.05 or P〈0.01).Compared with that in herceptin group,KRAS m RNA in middle-dose taxus chinensis+herceptin group was significantly decreased(0.036±0.007 vs 0.362±0.162,P〈0.01).Conclusion Taxus chinensis water extract can down regulate the expression of HER2,KRAS protein and m RNA via Ras/MAPK pathway in mice with gastric cancer.When it is combined with herceptin,its anti-tumor effect is enhanced.
出处
《浙江中西医结合杂志》
2016年第12期1074-1077,1081,共5页
Zhejiang Journal of Integrated Traditional Chinese and Western Medicine
基金
浙江省自然科学基金(No.LY13H290013)
浙江省中医药科技计划项目(No.2013ZA043)