Triple-negative breast cancer (TNBC) is a highly aggressive type of breast cancer and has a poor prognosis. As standardized TNBC treatment regimens cause drug resistance and tumor recurrence, the development of new TNBC treatment strategies is urgently required. Bufotalin is a bufadienolide isolated from the skin and parotid venom glands of the toad Bufo gargarizan, and has several pharmacological properties, including antiviral, anti-inflammatory, and anticancer activities. However, the anticancer effect and underlying molecular mechanisms of action of bufotalin in TNBC have not been fully studied. In the current study, we investigated the effects of bufotalin on the growth and metastasis of MDA-MB-231 and HCC1937 TNBC cells. Bufotalin potently inhibited the proliferation of both TNBC cell lines by promoting cell cycle arrest and caspase-mediated apoptosis. Furthermore, bufotalin effectively suppressed the migration and invasion of both TNBC cell lines by regulating the expression of key epithelial-mesenchymal transition (EMT) biomarkers, matrix metalloproteinases (MMPs), and integrin α6. Notably, the anticancer effect of bufotalin in TNBC cells was associated with the downregulation of the signal transducer and activator of the transcription 3 (STAT3) signaling pathway. Collectively, our results suggest that the natural compound bufotalin may exert antiproliferative and antimetastatic activities in TNBC cells by modulating the apoptotic pathway and the STAT3/EMT axis.

中文翻译：

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Bufotalin 通过促进细胞凋亡和抑制 STAT3/EMT 轴来抑制三阴性乳腺癌细胞的增殖和转移。

三阴性乳腺癌（TNBC）是一种高度侵袭性的乳腺癌，预后较差。由于标准化的TNBC治疗方案会导致耐药性和肿瘤复发，迫切需要开发新的TNBC治疗策略。Bufotalin 是从蟾蜍 Bufo gargarizan 的皮肤和腮腺毒腺中分离出来的蟾蜍二烯内酯，具有多种药理特性，包括抗病毒、抗炎和抗癌活性。然而，蟾蜍他林在TNBC中的抗癌作用和潜在分子机制尚未得到充分研究。在本研究中，我们研究了蟾蜍他林对MDA-MB-231和HCC1937 TNBC细胞生长和转移的影响。Bufotalin 通过促进细胞周期停滞和 caspase 介导的细胞凋亡，有效抑制两种 TNBC 细胞系的增殖。此外，蟾蜍他林通过调节关键上皮间质转化（EMT）生物标志物、基质金属蛋白酶（MMP）和整合素α6的表达，有效抑制两种TNBC细胞系的迁移和侵袭。值得注意的是，蟾蜍他林在 TNBC 细胞中的抗癌作用与信号转导子和转录 3 (STAT3) 信号通路激活子的下调有关。总的来说，我们的结果表明天然化合物蟾蜍他林可能通过调节细胞凋亡途径和 STAT3/EMT 轴在 TNBC 细胞中发挥抗增殖和抗转移活性。