乳腺癌 (BC) 是全球最常见的恶性肿瘤之一，但乳腺癌的药物开发一直面临着不断升级的挑战。没药是从没药 (T. Nees) Engl. 的干燥树脂中提取的，在中国广泛用于治疗 BC。然而，没药的抗 BC 作用和潜在机制仍不清楚。采用 MTT 法、EdU 法和集落形成法测定没药正己烷提取物 (CMHE) 对人 BC 增殖的影响细胞。通过流式细胞术分析评估细胞周期分布和凋亡。此外，使用伤口划痕试验和基质胶侵袭试验评估转移潜力。建立4T1乳腺癌小鼠模型以评价CMHE体内抗BC功效。通过RNA测序分析、实时定量PCR、免疫印迹、免疫组织化学分析、RNA干扰分析和数据库分析，揭示了CMHE抗BC作用的潜在机制。我们证明了CMHE对BC增殖能力的显着抑制作用细胞系 MDA-MB-231 和 MCF-7，由 CMHE 提供。此外，还观察到CMHE诱导上述两种BC细胞系G0/G1期停滞和凋亡。 CMHE 在体外显着抑制了这两种细胞的转移潜力。此外，给予 CMHE 显着抑制了 4T1 荷瘤小鼠的肿瘤生长。未发现 CMHE 对小鼠给药有明显的毒副作用。此外，免疫组织化学（IHC）分析表明，CMHE治疗抑制癌细胞的增殖和转移能力，同时还促进小鼠肿瘤组织的凋亡。基于RNA测序分析、实时定量PCR、免疫印迹和IHC测定，CMHE的施用下调了BC中的Cyclin D1/CDK4-Rb信号通路。此外，RNA干扰实验和数据库分析表明，下调的Cyclin D1/CDK4信号级联参与了CMHE的抗BC活性。CMHE治疗通过刺激细胞周期阻滞在G0/G1期，导致BC细胞生长受到抑制并通过抑制 Cyclin D1/CDK4-Rb 通路诱导细胞凋亡，从而增强 CMHE 的抗 BC 作用。 CMHE 具有潜在的抗 BC 作用，特别是在 Cyclin D1/CDK4-Rb 信号传导异常激活的细胞中。版权所有 © 2024 Huang、Xie、Wang、Jiao、Li、Wang、Liu、Wang、Wei、Tan、Tu、Li 和胡。

Breast cancer (BC) is one of the most frequently observed malignancies globally, yet drug development for BC has been encountering escalating challenges. Commiphora myrrha is derived from the dried resin of C. myrrha (T. Nees) Engl., and is widely adopted in China for treating BC. However, the anti-BC effect and underlying mechanism of C. myrrha remain largely unclear.MTT assay, EdU assay, and colony formation were used to determine the effect of C. myrrha n-hexane extract (CMHE) on the proliferation of human BC cells. Cell cycle distribution and apoptosis were assessed via flow cytometry analysis. Moreover, metastatic potential was evaluated using wound-scratch assay and matrigel invasion assay. The 4T1 breast cancer-bearing mouse model was established to evaluate the anti-BC efficacy of CMHE in vivo. RNA-sequencing analysis, quantitative real-time PCR, immunoblotting, immunohistochemical analysis, RNA interference assay, and database analysis were conducted to uncover the underlying mechanism of the anti-BC effect of CMHE.We demonstrated the significant inhibition in the proliferative capability of BC cell lines MDA-MB-231 and MCF-7 by CMHE. Moreover, CMHE-induced G0/G1 phase arrest and apoptosis of the above two BC cell lines were also observed. CMHE dramatically repressed the metastatic potential of these two cells in vitro. Additionally, the administration of CMHE remarkably suppressed tumor growth in 4T1 tumor-bearing mice. No obvious toxic or side effects of CMHE administration in mice were noted. Furthermore, immunohistochemical (IHC) analysis demonstrated that CMHE treatment inhibited the proliferative and metastatic abilities of cancer cells, while also promoting apoptosis in the tumor tissues of mice. Based on RNA sequencing analysis, quantitative real-time PCR, immunoblotting, and IHC assay, the administration of CMHE downregulated Cyclin D1/CDK4-Rb signaling pathway in BC. Furthermore, RNA interference assay and database analysis showed that downregulated Cyclin D1/CDK4 signaling cascade participated in the anti-BC activity of CMHE.CMHE treatment resulted in the suppression of BC cell growth through the stimulation of cell cycle arrest at the G0/G1 phase and the induction of apoptotic cell death via the inhibition of the Cyclin D1/CDK4-Rb pathway, thereby enhancing the anti-BC effect of CMHE. CMHE has potential anti-BC effects, particularly in those harboring aberrant activation of Cyclin D1/CDK4-Rb signaling.Copyright © 2024 Huang, Xie, Wang, Jiao, Li, Wang, Liu, Wang, Wei, Tan, Tu, Li and Hu.