补中益气汤通过SHP-1对转移性乳腺癌TAM耐药性的影响

The effect of Buzhongyiqitang on the TAM drug resistance of metastatic breast cancer through SHP-1

目的研究补中益气汤(BZYQT)通过SHP-1对转移性乳腺癌TAM耐药性的影响。方法TAM培养液持续培养6个月产生耐TAM人乳腺癌细胞系MCF-7/TAM-R。RNA干扰构建抑制SHP-1的乳腺癌细胞系MCF-7/TAM-R^(SHP-1 Ri)和阴性对照细胞系MCF-7/TAM-R^(NC),接种两种细胞于裸鼠建立乳腺癌肺转移瘤模型,然后给予补中益气汤处理。实验分4组,MCF-7/TAM-R^(NC)、MCF-7/TAM-R^(SHP-1 Ri)、BZYQT+MCF-7/TAM-R^(NC)、BZYQT+MCF-7/TAM-R^(SHP-1 Ri)。观察裸鼠肿瘤生长;Western blot和q PCR检测SHP-1、EGFR、HER-2蛋白含量及基因表达。结果与MCF-7/TAM-R^(NC)组相比,BZYQT+MCF-7/TAM-R^(NC)组的SHP-1基因表达及蛋白含量上升,EGFR基因表达及蛋白含量下降,HER-2蛋白含量下降,肿瘤体积变小。MCF-7/TAM-R^(SHP-1 Ri)组的EGFR基因表达及蛋白含量上调,HER-2蛋白含量上升,肿瘤生长迅速,体积变大;BZYQT+MCF-7/TAM-R^(SHP-1 Ri)组的肿瘤生长得以部分抑制,EGFR和HER-2蛋白相应下调,EGFR基因表达也相应下调。结论补中益气汤通过上调SHP-1而抑制EGFR基因及蛋白和HER-2蛋白表达,逆转MCF-7细胞对TAM耐药,进一步抑制肿瘤的生长。

Objective To study the effects of Buzhongyiqitang on the TAM drug resistance of metastatic breast cancer through SHP - 1. Methods That TAM was added in culture medium for more than six months to induce drug - resistant breast cancer cell model MCF - 7/TAM - R. The experiment groups were divided into MCF - 7/TAM - RNC, MCF - 7/TAM - RSHP-1 Ri, BZYQT ＋ MCF - 7/TAM - RNC and BZYQT ＋ MCF - 7/TAM - RsliP- 1 Ri SHP - 1 was inhibited by RNA interference in breast cancer cell line MCF - 7/TAM - RSHP- 1 Ri. And MCF - 7/TAM - RNc was applied as negative control cell line. The two cell lines were inoculated in nude mice to establish the model of lung metastasis of breast cancer, and Buzhongyiqitang treatment was given. The tumor growth in nude mice was recorded. SHP - 1, EGFR and HER - 2 protein and mRNA expression were assessed by western - blot and qPCR, respectively. Results Compared with MCF - 7/TAM - RNC group, the gene expression and protein expression of SHP - 1 were increased ; the gene expression and protein expression of EGFR decreased; the protein expression of HER -2 decreased; and the tumor size was smaller in BZYQT ＋ MCF - 7/TAM - RNC group. Compared with MCF - 7/TAM - RNC group, the gene expression and protein expression of EGFR increased; the protein expression of HER -2 increased; and the tumor size was bigger in MCF - 7/TAM - RSHP-L Ri group. Compared with MCF - 7/TAM - RNC group, the tumor growth was partially suppressed, the protein expression of EGFR and HER - 2 increased, and the gene expression of EGFR decreased in BZYQT ＋ MCF - 7/ TAM - RSHF- RNC group. Conclusion Buzhongyiqitang inhibits the gene expression and protein expression of EGFR, and the protein expression of HER - 2 by up - regulating the expression of SHP - 1, and thus further reverses the TAM drug resistance of the MCF -7 cell and inhibits the tumor growth.