Breast cancer is one of the most common and deadly cancers in women worldwide. Current treatments for breast cancer have limitations, such as toxicity, resistance, and side effects. Therefore, there is a need to develop new and effective anti-cancer agents from natural sources. Spinosyn A (SPA) is a natural product derived from soil bacteria. SPA has been reported to have anti-parasitic, insecticidal, and anti-bacterial activities. However, its anti-cancer effects and mechanisms are not well understood. In this study, we investigated the effects of SPA on T47-D, estrogen receptor-positive breast cancer cells. We found that SPA inhibited cell proliferation and migration and induced apoptosis and cell cycle arrest. Flow cytometry and holographic imaging microscopy revealed that SPA activated MAPK and PI3K signaling pathways and altered cellular morphology. Finally, RNA-Seq analysis revealed that SPA treatment altered the expression of 1380 genes in T47-D cells, which were enriched in various biological processes and signaling pathways related to cell proliferation, cholesterol metabolism, growth factor activity, amino acid transport activity, extracellular matrix, PI3K-Akt signaling pathway, neuroactive ligand-receptor interaction, and PPAR signaling pathway. Our results suggest that SPA exerts multiple anti-cancer effects on T47-D cells by modulating multiple pathways and cellular processes involved in cell growth, survival, and motility. Our findings provide new insights into the molecular mechanisms of SPA action on breast cancer cells and its potential applications as a novel anti-cancer agent.

中文翻译：

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Spinosyn A 通过调节多种信号通路对孕酮敏感的 ERα 阳性乳腺癌细胞发挥抗肿瘤作用


乳腺癌是全世界女性最常见和致命的癌症之一。目前乳腺癌的治疗方法存在局限性，例如毒性、耐药性和副作用。因此，需要从天然来源开发新的有效的抗癌剂。 Spinosyn A (SPA) 是一种源自土壤细菌的天然产物。据报道，SPA 具有抗寄生虫、杀虫和抗菌活性。然而，其抗癌作用和机制尚不清楚。在这项研究中，我们研究了 SPA 对雌激素受体阳性乳腺癌细胞 T47-D 的影响。我们发现SPA抑制细胞增殖和迁移并诱导细胞凋亡和细胞周期停滞。流式细胞术和全息成像显微镜显示 SPA 激活 MAPK 和 PI3K 信号通路并改变细胞形态。最后，RNA-Seq分析显示，SPA处理改变了T47-D细胞中1380个基因的表达，这些基因富含与细胞增殖、胆固醇代谢、生长因子活性、氨基酸转运活性、细胞外代谢相关的各种生物过程和信号通路。基质、PI3K-Akt 信号通路、神经活性配体-受体相互作用和 PPAR 信号通路。我们的结果表明，SPA 通过调节涉及细胞生长、存活和运动的多种途径和细胞过程，对 T47-D 细胞发挥多种抗癌作用。我们的研究结果为 SPA 对乳腺癌细胞作用的分子机制及其作为新型抗癌剂的潜在应用提供了新的见解。