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

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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 investigate the anti-tumor effect and mechanism of ginsenoside Rg3 combined with suramin on Lewis lung carcinoma in mice. Methods: Lewis lung cancer mouse model was established and divided into control group, cisplatin group, ginsenoside Rg3 group, suramin group, ginsenoside Rg3 + suramin combination group. After the intervention of drug for 16 days, the transplanted tumor was dissected, , The tumor inhibition rate was calculated. The expression of CD34 on the transplanted tumor was measured by immunohistochemistry, and the expression of MEK1 / 2 and ERK1 / 2 mRNA was detected by RT-PCR. MEK1 / 2, ERK1 / 2 and p-ERK1 / 2 (phosphorylated ERK1 / 2) protein expression. Results: The tumor inhibition rates of cisplatin group, ginsenoside Rg3 group, suramin group and ginsenoside Rg3 + suramin combination group were 19.7%, 35.4%, 35.9% and 49.4%, respectively; the MVD counts of control group and drug intervention group were respectively 24.06 ± 2.40, 19.41 ± 1.98, 13.06 ± 1.92, 12.09 ± 1.49 and 6.16 ± 1.17, respectively. The MVD of each drug intervention group was lower than that of the control group, the difference was statistically significant (P <0.01). The relative amounts of ERK1 / 2 mRNA were (71.93 ± 13.47)%, (56.43 ± 11.01)%, (45.27 ± 8.82)%, (43.29 ± 7.48)% and (104.18 ± 9.78)%, (84.61 ± 7.66)%, (76.71 ± 7.25)%, (74.01 ± 7.41)% and (51.69 ± 5.29)%, respectively. The relative amounts of p-ERK1 / 2 protein were (112.96 ± (87.86 ± 6.77)%, (61.26 ± 8.48)%, (38.60 ± 10.66)% and (9.57 ± 3.42)%, respectively. The mRNA and protein expressions of ERK1 / 2 and p-ERK1 / Were lower than the control group, and the combination group decreased significantly, the difference was statistically significant, P <0.01. Conclusion: Ginsenoside Rg3 and suramin can inhibit the growth of Lewis lung carcinoma in mice, and the combined effect of the two drugs is more obvious. The mechanism may be related to the inhibition of extracellular signal kinase pathway and angiogenesis.
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