黄芪、莪术配伍联合奥沙利铂对CT26.WT原位移植瘤小鼠中CXCR3、CCR6表达影响

Effects of Huangqi and Ezhu combined with oxaliplatin on CXCR3 and CCR6 expression in mice with CT26. WT orthotopically transplanted tumor

目的探讨中药扶正祛邪药对——黄芪、莪术粗提物与奥沙利铂(L-OHP)联合应用抑制鼠结肠癌CT26 wild-type(CT26.WT)细胞的转移,调控CXCR3、CCR6 mRNA及蛋白表达的作用。方法首先构建BALB/c结肠癌原位移植瘤小鼠模型,之后运用L-OHP(0.1 mg/次,隔日1次)单独以及联合黄芪、莪术粗提物高、中、低剂量(6、3、1.5 g/kg)作用于结肠癌模型小鼠,观察模型小鼠肝转移情况及运用RT-PCR测定CXCR3、CCR6 mRNA表达,Western Blot检测CXCR3、CCR6蛋白表达。结果 L-OHP单独应用和联合中药应用均能抑制原位移植瘤体的增大,阳性药抑制原位移植瘤生长的效果最好(P<0.01)。联合用药能降低肝转移灶的发生(P<0.05)。与空白对照组相比,阳性组及联合用药低剂量组CXCR3及CCR6 mRNA的表达显著下调(P<0.01),联合用药能不同程度下调CXCR3、CCR6蛋白表达(P<0.05,P<0.01)。结论黄芪、莪术联合化疗药抗肿瘤转移机制可能与下调CXCR3、CCR6 mRNA及蛋白相关。

Objective To investigate the effects of extract from couple medicinals of strengthening healthy qi and eliminating pathogenic qi, i.e.Huangqi（Radix Astragali, astragalus root） and Ezhu （Rhizoma Curcumae, curcumae rhizome）, and oxaliplatin（L-OHP）on inhibiting metastasis of CT26 wild-type（CT26.WT）cells, and regulating CXCR3, CCR6 mRNA, and protein expression in rats with colon cancer.Methods Orthotopic transplantation model of BALB/c colon carcinoma was built in mice.L-OHP or L-OHP combined with extract from huangqi and ezhu were given to the mice model.Effects of those medicines on liver metastasis were observed.CXCR3 and CCR6 mRNA expression were measured by using RT-PCR, and CXCR3, CCR6 protein expression was detected with Western Blot.Results L-OHP group and L-OHP combined with Chinese medicinal groups exhibited inhibitive effects on orthotropic tumor growth, and best effect was observed in positive expression （P〈0.01）.L-OHP combined with TCM can decrease the incidence of liver metastasis （P〈0.05）.Compared with the control group, mRNA expressions of CXCR3 and CCR6 decreased in the model group and low-dose group （P〈0.01）.Effects of L-OHP combined with low-dose Chinese medicine were more effective than other groups（P〈0.01）.Compared with the control group, CXCR3 and CCR6 protein expressions decreased sinificantly in all groups（P〈0.05 or P〈0.01）.Conclusion Mechanism of huangqi, ezhu and oxaliplatin（L-OHP） to inhibit tumor metastasis may relate to downregulation of CXCR3, CCR6 mRNA and protein expression.