蒲公英提取物通过CUEDC2影响三阴乳腺癌干细胞干性抑制其恶性表型的分子机制

Triple-negative breast cancer (TNBC) has the worst prognosis among all subtypes of breast cancer. It has specific biological characteristics and clinicopathological features, contains a high proportion of breast cancer stem cells (BCSCs), with higher tumor heterogeneity, invasiveness, local recurrence¬ and distant metastases, thus become a hot topic in breast cancer research. Our previous study showed CUEDC2 is expressed in triple-negative breast cancer and associated with its malignant phenotype. Knockdown or overexpression of CUEDC2 affects TNBC stem cell mammosphere formation ability and cancer stem cell markers expression.The mammary gland is the circulation part of liver channel, and dandelion is an important Chinese herb to treat breast disease with the characteristic of distributing to live channel. The dandelion extract can inhibit the growth and invasion of TNBC, reduce the expression of CUEDC2 and cancer stem cell markers.This project intends to study the biological function of CUEDC2 in TNBC, the regulation of stemness of tumor stem cells and its correlation with clinical prognosis, and to determine whether CUEDC2 is a key molecule for dandelion to exert inhibitory effect in TNBC. In this project, it has a tight combination between the theory of Traditional Chinese medicine and modern research technology. We chose breast cancer as the subject to study as dandelion distributes to live channel according to the theory of channel tropism theories. The results of present project will provide scientific basis for dandelion as an effective herb drug to treat TNBC, offer new ideas for the treatment of TNBC, give scientific support for the theory of “dandelion is an important herb for the treatment of breast disease” , therefore, it has important theoretical significance and application value.

三阴乳腺癌（TNBC）是预后最差的一种乳腺癌，具有独特的生物学特性和临床病理特征，富含肿瘤干细胞，肿瘤异质性高，局部复发及远处转移率较高，是乳腺癌研究关注的焦点。本项目前期研究发现：CUEDC2蛋白在TNBC表达且与其恶性表型相关，与β-catenin存在相互作用，能调节TNBC干细胞微球形成能力及干细胞标志物的表达。中药蒲公英提取物能抑制TNBC的生长和侵袭，降低CUEDC2及肿瘤干细胞标志物的表达。本项目拟研究CUEDC2在TNBC中的生物学功能、对肿瘤干细胞干性的调控作用，明确CUEDC2是否为蒲公英提取物抑制TNBC的关键分子。本项目密切结合中医药传统理论与现代科学研究方法，根据中药归经理论，选择蒲公英所入肝经的循行部位（乳腺）肿瘤为研究对象，为蒲公英治疗TNBC提供科学依据，给TNBC的治疗提供新的思路，给“蒲公英为治疗乳疾要药”的理论进行科学支撑，具有重要的理论意义和应用价值。

三阴乳腺癌（TNBC）是预后最差的一种乳腺癌，具有独特的生物学特性和临床病理特征，富含肿瘤干细胞，肿瘤异质性高，局部复发及远处转移率较高，是乳腺癌研究关注的焦点。探索三阴乳腺癌的治疗药物及其抑制肿瘤的分子机制具有重要意义。本研究发现：CUEDC2蛋白在TNBC表达且与其恶性表型相关，与β-catenin存在直接相互作用，促进β-catenin核转位启动下游信号转录，能调节TNBC干细胞微球形成能力及干细胞标志物的表达，明确了CUEDC2通过与β-catenin的交互作用参与调控三阴乳腺癌细胞干性表型，二者的表达与三阴乳腺癌的临床预后具有相关性，靶向CUEDC2-β-catenin相互作用具有治疗潜力。中药蒲公英提取物能抑制TNBC在体内外的生长能力等恶性表型，下调CUEDC2及β-catenin的表达，抑制三阴乳腺癌干细胞的干性特征，阐明蒲公英提取物通过调控 CUEDC2 影响三阴乳腺癌干细胞干性抑制其恶性表型的分子机制。本课题的研究结果为蒲公英治疗TNBC提供科学依据，给TNBC的治疗提供新的思路，给“蒲公英为治疗乳疾要药”的理论进行科学支撑，具有重要的理论意义和应用价值。