阿帕替尼通过ERK/JAK2-STAT3途径对MDA-MB-468荷瘤动物模型肿瘤细胞生长抑制和凋亡的影响及其作用机制探讨

Effects of apatinib on tumor cell growth inhibition and apoptosis in MDA-MB-468 tumor bearing animal model through ERK/JAK2-STAT3 pathway and its mechanism

目的:探究阿帕替尼(APA)通过ERK/JAK2-STAT3途径对三阴性乳腺癌(TNBC)模型的影响和作用机制。方法:通过皮下注射MDA-MB-468细胞构建荷瘤裸鼠模型,随机分为对照组、低剂量阿帕替尼组(4.15 mg·kg^(-1),灌胃)和高剂量APA组(8.30 mg·kg^(-1),灌胃),每组各6只。比较各组细胞凋亡、增殖、ERK/JAK2-STAT3水平。结果:高剂量APA组抑瘤率为(31.37±1.95)%,高于低剂量APA组。高剂量APA组细胞凋亡率为(24.52±3.27)%,显著高于低剂量APA组和对照组,P<0.05。高剂量APA组Ki-67染色评分为(4.63±1.26)分,显著低于低剂量APA组和对照组,P<0.05。低剂量APA组和高剂量APA组的血管内皮生长因子受体-2(VEGFR-2)、ERK/JAK2-STAT3途径显著低于对照组(P<0.05)。高剂量APA组的VEGFR-2蛋白水平显著低于低剂量APA组(P<0.05)。结论:阿帕替尼可能通过抑制ERK/JAK-STAT通路抑制TNBC进展。

Objective:To explore the effect and mechanism of apatinib(APA)on the triple negative breast cancer(TNBC)model through ERK/JAK2-STAT3 pathway.Methods:The tumor-bearing nude mice model of TNBC was constructed by subcutaneously injecting MDA-MB-468 cells.All the mice were randomly divided into control group,low-dose APA group(4.15 mg·kg^(-1),gavage)and high-dose APA group(8.30 mg·kg^(-1),gavage)with 6 rats in each group.The levels of apoptosis and proliferation of turmor cells,and ERK/JAK2-STAT3 levels in each group were compared.Results:The tumor inhibition rate in the high-dose APA group(31.37±1.95)%was higher than that in the low-dose APA group.The apoptosis rate in the high-dose APA group was(24.52±3.27)%,which was signifi cantly higher than that in the low-dose APA group and the control group,P<0.05.The Ki-67 staining score of the high-dose APA group was(4.63±1.26),which was signifi cantly lower than that of the low-dose APA group and the control group,P<0.05.The levels of VEGFR-2 and ERK/JAK2-STAT3 in the low-dose APA group and the high-dose APA group were signifi cantly lower than those in the control group(P<0.05).The VEGFR-2 protein level in the high-dose APA group was signifi cantly lower than that in the low-dose APA group(P<0.05).Conclusion:Apatinib may inhibit the progression of TNBC by inhibiting the ERK/JAK-STAT pathway.