人参皂苷Rg3联合苏拉明对小鼠肺癌生长影响及其机制的探讨

Effects of Ginsenoside Rg3 in combination with Suramin on growth of lung cancer in mice

目的:探讨人参皂苷Rg3联合苏拉明对小鼠Lewis肺癌移植瘤的抑瘤作用及机制。方法:建立Lewis肺癌小鼠模型后,分为对照组、顺铂组、人参皂苷Rg3组、苏拉明组、人参皂苷Rg3+苏拉明联合组,药物干预16d后,剥离移植瘤,称瘤质量,计算抑瘤率;免疫组化法测定各组移植瘤CD34的表达即肿瘤微血管密度(MVD)测定;逆转录PCR法测移植瘤MEK1/2和ERK1/2的mRNA;蛋白质印迹法测MEK1/2、ERK1/2及p-ERK1/2(磷酸化ERK1/2)蛋白的表达。结果:顺铂组、人参皂苷Rg3组、苏拉明组和人参皂苷Rg3+苏拉明联合组抑瘤率分别为19.7%、35.4%、35.9%和49.4%;对照组和药物干预组MVD计数分别为24.06±2.40、19.41±1.98、13.06±1.92、12.09±1.49和6.16±1.17,各药物干预组MVD较对照组低,差异有统计学意义,P<0.01。各组ERK1/2mRNA相对量分别为(71.93±13.47)%、(56.43±11.01)%、(45.27±8.82)%、(43.29±7.48)%和(28.75±5.41)%,ERK1/2蛋白相对量分别为(104.18±9.78)%、(84.61±7.66)%、(76.71±7.25)%、(74.01±7.41)%和(51.69±5.29)%,p-ERK1/2蛋白相对量分别为(112.96±9.49)%、(87.86±6.77)%、(61.26±8.48)%、(38.60±10.66)%和(9.57±3.42)%,ERK1/2、p-ERK1/2在各药物干预组的mRNA及蛋白的表达均低于对照组,且联合组降低明显,差异有统计学意义,P<0.01。结论:人参皂苷Rg3、苏拉明具有抑制小鼠Lewis肺癌生长的作用,且两药联用作用更明显,其机制可能与抑制细胞外信号激酶通路及血管生成有关。

OBJECTIVE:To evaluate the inhibitory efficacy of the combination of Ginsenoside Rg3 and Suramin on the growth of the Lewis lung cancer in mice.METHODS: Forty C57BL6 mice bearing Lewis lung carcinoma were randomized into several groups,and received cisplatin 3 mg/(kg·5 d),ginsenoside Rg3 5 mg/(kg·d),suramin 10 mg/(kg·d),ginsenoside Rg3 combined with suramin therapy respectively for 16 days.The transplanted tumor weight and the tumor inhibiting rate were measured in every group.The tumor microvascular density(MVD) was detected by immunohistochemistry,and the expression of MEK1/2,ERK1/2,and p-ERK1/2 were detected by RT-PCR and western blot.RESULTS: After treated with cisplatin,suramin,ginsenoside Rg3,ginsenoside Rg3 combined with suramin respectively,the growth of transplanted tumor was inhibited markedly.The tumor inhibitory rate was 19.7%,35.4%,35.9% and 49.4% in the cisplatin,suramin,ginsenoside Rg3,ginsenoside Rg3 combined with suramin therapy group respectively.In the control group,and every therapy group,the expression of MVD were 24.06±2.40,19.41±1.98,13.06±1.92,12.09±1.49 and 6.16± 1.17,respectively.The ERK1/2mRNA were(71.93±13.47)%,(56.43±11.01)%,(45.27±8.82)%,(43.29±7.48)% and(28.75±5.41)%,respectively.The ERK1/2 protein were(104.18±9.78)%,(84.61±7.66)%,(76.71±7.25)%,(74.01±7.41)% and(51.69±5.29)%,respectively,and the p-ERK1/2 protein were(112.96±9.49)%,(87.86±6.77)%,(61.26±8.48)%,(38.60±10.66)% and(9.57±3.42)%,respectively.The MVD was decreased significantly in therapy groups,especially in the combination group(P<0.01).Compared with the control group,the expression of the ERK1/2 and p-ERK1/2 was down-regulated in the four therapy groups,and especially in the combination group whether at the mRNA or protein level(P<0.01).CONCLUSION: The results indicates that Suramin combined with Ginsenoside Rg3 can inhibite the growth of Lewis lung cancer more effectively in mice,which possibly is related to inhibite the angiogenesis via suppressing the Extracellular Signal Kinase Pathway.