The incidence and mortality of breast cancer (BCa) are the highest among female cancers. There are approximate 70% BCa that are classified as estrogen receptor alpha (ERα) positive. Therefore, targeting ERα is the most significantly therapeutic schedule. However, patients with breast cancer develop resistance to ERα or estrogen (E2) antagonists such as fulvestrant and tamoxifen. In the present study, we found that L-Tetrahydropalmatine (L-THP) significantly suppressed cell proliferation in ERα+ BCa cells via inducing cell cycle arrest rather than apoptosis. Additionally, L-THP enhanced the sensitivity of ERα+ BCa cells to tamoxifen and fulvestrant. Mechanically, the application of L-THP promotes ERα degradation through accumulating ubiquitin chains on ERα. Overexpressing ERα abrogates L-THP induced-antiproliferation in ERα+ BCa cells. Collectively, our work indicates that L-THP may represent a potentially novel therapeutic medicine for ERα+ breast cancer patient.

中文翻译：

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L-四氢巴马汀靶向 ERα 降解为乳腺癌治疗提供了一种新策略。

乳腺癌（BCa）的发病率和死亡率是女性癌症中最高的。大约 70% 的 BCa 被归类为雌激素受体α (ERα) 阳性。因此，靶向 ERα 是最重要的治疗方案。然而，乳腺癌患者对 ERα 或雌激素 (E2) 拮抗剂如氟维司群和他莫昔芬产生耐药性。在本研究中，我们发现 L-四氢巴马汀 (L-THP) 通过诱导细胞周期停滞而不是细胞凋亡显着抑制 ERα+ BCa 细胞的细胞增殖。此外，L-THP 增强了 ERα+ BCa 细胞对他莫昔芬和氟维司群的敏感性。从机制上讲，L-THP 的应用通过在 ERα 上积累泛素链来促进 ERα 降解。过表达 ERα 消除了 ERα+BCa 细胞中 L-THP 诱导的抗增殖。总的来说，