Abstract
Endocrine therapy is one of the main treatments for breast cancer patients in the early stages. Tamoxifen and fulvestrant are the major drugs of endocrine therapy for breast cancer patients. However, acquired drug resistance often caused treatment failure and relapse for patients, which is a major clinical problem. We investigated whether Huaier extract had effects on endocrine-resistant breast cancer cells. In our study, we aimed to demonstrate the inhibitory effects of Huaier extract on tamoxifen-resistant cells (M7-TR) and fulvestrant-resistant cells (M7-FR). Using MTT and clone formation assays, we found that Huaier extract could inhibit the proliferation in M7-TR and M7-FR cells. Flow cytometry and western blotting illustrated that Huaier extract could induce G0/G1 arrest in both endocrine-resistant breast cancer cells. Mechanistically, we present that Huaier extract significantly increased ataxia telangiectasia mutation (ATM) via down-regulation of miR-203. Huaier extract also had the inhibitory effects on tumour growth in vivo in a xenograft mouse model. These results demonstrated that Huaier extract could inhibit the proliferation of M7-TR and M7-FR cells by increasing ATM via suppression of miR-203.
Highlights
Breast cancer has become the most common malignancy in women in a variety of countries
We revealed that Huaier extract, which has been widely used for antitumour effects in several cancers, inhibited proliferation in endocrine-resistant breast cancer cells
Accumulating evidence has underscored that Traditional Chinese medicine (TCM) is a rich source for finding new drugs, and increasingly, TCM has been found to have anti-tumour effects on cancer[25, 26]
Summary
Breast cancer has become the most common malignancy in women in a variety of countries. 75% of women with breast cancer are hormone receptor positive, expressing estrogen receptor (ER), and endocrine therapies are effective for patients with ER-positive breast cancer[2]. The selective estrogen receptor modulator (SERM) tamoxifen (TAM)[3] and selective estrogen receptor down-regulator (SERD) fulvestrant[4] are the major endocrine therapy drugs for breast cancer patients in early stages. Several mechanisms of the anti-tumour effects of Huaier extract were demonstrated, such as anti-angiogenesis, reversal of drug-resistance, radiosensitization, anti-metastasis and activation of the immune system[6, 8,9,10,11]. Extract demonstrated proliferation-inhibiting effects related to the cell cycle and DNA damage. We further investigated the roles of miR-203 and ATM in endocrine-resistant breast cancer cells after Huaier extract treatment
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