Anthocyanins potentiate the activity of trastuzumab in human epidermal growth factor receptor 2-positive breast cancer cells in vitro and in vivo
Anthocyanins potentiate the activity of trastuzumab in human epidermal growth factor receptor 2-positive breast cancer cells in vitro and in vivo
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DOI：
10.3892/mmr.2014.2414
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发表时间：
2014-10-01
影响因子：
3.4
通讯作者：
Li, Xin
中科院分区：
文献类型：
--
作者：
Liu, Weihua;Xu, Jinmei;Li, Xin
人类表皮生长因子受体2 （HER2）在大约25%的浸润性乳腺癌中被发现过表达，并且与乳腺癌患者的不良预后显著相关。花青素花青素-3-葡萄糖苷（C3G）和芍药苷-3-葡萄糖苷已被确定为治疗her2阳性乳腺癌的潜在药物。在亚洲，它们已被用作靶向治疗和化疗的补充，然而，其潜在的机制仍有待阐明。本研究的目的是研究C3G和曲妥珠单抗（Trast）之间的协同作用。为了解决这个问题，在三个代表性的her2阳性细胞系中评估了C3G， Trast和两种药物联合的反应。联合处理可诱导MDA-MB-453、BT474和HCC1569细胞凋亡，抑制细胞生长，影响HER2及其下游信号通路，且具有协同作用。在体内异种移植瘤模型中，3CG和Trast联合使用可抑制肿瘤生长。本研究的数据表明，C3G在实验条件下与Trast联合使用时显示出强大的抗肿瘤活性。
Human epidermal growth factor receptor 2 (HER2) has been found to be overexpressed in similar to 25% of invasive breast cancer and is significantly associated with a poor prognosis in breast cancer patients. The anthocyanins cyanidin-3-glucoside (C3G) and peonidin-3-glucoside have been identified as potential drugs for the therapy of HER2-positive breast cancer. They have been used as supplements in targeted therapeutics and chemotherapeutics in Asia, however, the underlying mechanism remains to be elucidated. The aim of the present study was to investigate the synergism between C3G and trastuzumab (Trast). To address this question, the response to C3G, Trast and a combination of the two drugs, in three representative HER2-positive cell lines was evaluated. The combination treatments induced apoptosis, inhibited cell growth and affected HER2 and its downstream signaling pathway in MDA-MB-453, BT474 and HCC1569 cells, and the effects were synergistic. The combination of 3CG and Trast inhibited tumor growth in an in vivo xenograft model. The data from the present study suggested that C3G exhibits potent antitumor activity when combined with Trast under the investigated conditions.