基于ER/EGFR途径交互调控探讨"白毛夏枯草-茯苓"药对治疗乳腺癌转移疗效与不同分子表型差异的相关性

Breast cancer is the most common cancer in women, and its associated metastases are the major cause of morbidity or mortality."Tandu Liuzhu"(stagnation of phlegm and vestigial poison invasion elsewhere) of the key pathogenesis of metastasis and recurrence of breast cancer. Our previous experiments showed that the active fractions from Ajugae and Poriacocos are mutually assisted to inhibit the proliferation, metastasis and prevent relapse of breast cancer, and this effect was associated with the molecular subtypes. In present study, targeting the crosstalk between estrogen receptor and EGFR pathways, we detected the antimetastatic effect of the combination of Ajugae and Poriacocos on different subtypes of breast cancer (including Luminal, HER2 enriched and basal cell like breast cancer). Furthermore, we evaluated the association of the different effects of TCM with the ER/EGFR signaling crosstalk. In all, this study is expected to provide evidence for the rational administration of "disintoxication and dispelling dampness" method in clinic, contributes to exploring the individualized therapy for breast cancer and deepens our understanding of the scientific meanings of compatibility of TCM.

中医理论认为"热毒内蕴，痰毒流注"是乳腺癌转移复发的核心病机，其分子基因表型与中医辨证分型和肿瘤转移复发密切相关。本实验室前期研究发现具有"清热解毒、利湿化痰"功效的药对"白毛夏枯草-茯苓"对乳腺癌转移复发有明显治疗作用；且此作用与乳腺癌ER、HER2和EGFR的表达状态相关。本研究拟采用不同分子表型的乳腺癌细胞株模拟临床上目前普遍认知和接受的不同乳腺癌分子分型（Luminal型，HER2过表达型和Basal like/三阴性型），探讨药对"白毛夏枯草-茯苓"对不同分子亚型乳腺癌细胞生物学行为和器官转移倾向性的影响与ER/EGFR交互调控信号途径靶蛋白之间的相关性，阐明此药对治疗不同分子亚型乳腺癌疗效差异的分子机制，为其临床用于治疗乳腺癌转移提供实验依据，并为针对不同分子基因表型的个体化治疗提供用药依据；亦可为深化中药复方配伍理论的认识做出有意义的探索。