健脾复方通过Wnt/β-catenin信号通路抑制裸鼠人大肠癌转移

摘要

目的：研究中药健脾复方通过Wnt/β-catenin信号通路抑制裸鼠人大肠癌转移的机制。方法建立人肠癌HT29细胞裸鼠皮下移植瘤模型，随机分为5组：模型组（生理盐水组），健脾复方低、中、高剂量组[0.25，0.5，1mL/d]和5氟尿嘧啶组[1mg/(kg·2d)]。给药第21天，各组均处死荷瘤鼠，测量肿瘤质量。采用免疫组化法检测各组瘤体的β-catenin表达。Elisa检测裸鼠血清MMP-7表达。结果健脾复方低、中、高剂量组的瘤重抑制率分别为23.49%、45.64%、65.77%。免疫组化结果显示，健脾复方能够以剂量依赖性方式下调肿瘤组织β-catenin蛋白表达。Elisa结果显示，健脾复方低、中、高剂量组裸鼠血清MMP-7表达量分别是模型组的0.84、0.62和0.45倍，差异具有统计学意义（P＜0.01）。结论健脾复方能抑制人结肠癌裸鼠皮下移植瘤的转移，其机制可能是通过Wnt/β-catenin信号通路下调MMP-7表达有关。%Objective To study effects of Jianpi Complex Prescription to hypodermatic transplanted tumor metastasis in colorectal cancer nude mice. Methods Colorectal cancer models in nude mice bear human HT-29 cells were established,and then were randomLy divided into 5 groups: Control group (NS control group),Jianpi Complex Prescription low-dose,mid-dose,high-dose group (0.25,0.5,1mL/d),5-FU group (1 mg/kg·2d).All group of nude mice were sacrificed at the last time treatment for 21 days,the size and weight of tumor were measured.Theβ-catenin was tested by Immunohistochemistry; the MMP-7 expression in mice serum was assayed by ELISA. Results The inhibition rate of tumor in each group were respectively 23.49%,45.64%,65.77% in low,mid,and high-dose Jianpi Complex Prescription.Jianpi Jiedu Recipe dose-dependently reduced the level of β-catenin in mice tumor.The MMP-7 in low,mid,high-dose Jianpi Jiedu Recipe was obviously decreased compared with Control group(P<0.01). Conclusion Jianpi Complex Prescription could inhibited the metastasis of colon carcinoma implant tumor of nude mice, which may be due to blocking Wnt/β-catenin signal pathway and reducing MMP-7 expression.