Department of Cellular and Molecular Biology, Kish International Campus, University of Tehran, Kish, Iran.
Department of Cellular and Molecular Biology, School of Biology, College of Science, University of Tehran, Tehran, 14155-6455, Iran.
Mol Biotechnol. 2023 Dec;65(12):1979-1990. doi: 10.1007/s12033-023-00702-5. Epub 2023 Mar 11.
This study aimed to evaluate the comparative effect of silibinin (SB) on the expression of MiR‑20b and BCL2L11 in T47D and MCF-7 cell lines. Molecular simulation studies were carried out to analyze Erbb2, as a potential target of SB, to direct the breast cancer cells toward apoptosis. At first, cell viability, apoptosis, and cell cycle arrest-inducing capacity of SB were examined using MTT and flow cytometry analysis, respectively. Real-time PCR (RT-PCR) was employed to assess the effect of SB on BCL2L11, Phosphatase and tensin homolog (PTEN), and Caspase 9 mRNarrest-indu. Moreover, alterations in Caspase 9 protein expression were determined using Western blot analysis. Finally, AutoDockVina software was used to dock the SB/ MiR‑20b and SB/ erb-b2 receptor tyrosine kinase 2 (Erbb2) interaction. The obtained data revealed the potent cytotoxicity of SB in both T47D and MCF-7 cells through apoptosis induction and cell cycle arrest. SB-treated cells also showed downregulation of MiR‑20b and high expression of BCL2L11, PTEN, and Caspase 9 mRNA compared to non-treated cancer cells. Computational docking showed a strong interaction between SB/ MiR‑20b and SB/Erbb2. It can be concluded that SB had a strong anti-tumorigenic activity through BCL2L11upregulation and MiR‑20b down expression, maybe through targeting the PTEN and interacting with Erbb2, which resulted in apoptotic induction and cell cycle arrest.
本研究旨在评估水飞蓟宾(SB)对 T47D 和 MCF-7 细胞系中 miR-20b 和 BCL2L11 表达的比较影响。进行了分子模拟研究,以分析 Erbb2 作为 SB 的潜在靶标,将乳腺癌细胞导向细胞凋亡。首先,通过 MTT 和流式细胞术分析分别检测 SB 对细胞活力、细胞凋亡和细胞周期阻滞的影响。实时 PCR(RT-PCR)用于评估 SB 对 BCL2L11、磷酸酶和张力蛋白同源物(PTEN)和 Caspase 9 mRNA 的影响。此外,使用 Western blot 分析测定 Caspase 9 蛋白表达的变化。最后,使用 AutoDockVina 软件对接 SB/miR-20b 和 SB/erb-b2 受体酪氨酸激酶 2(Erbb2)相互作用。获得的数据表明,SB 通过诱导细胞凋亡和细胞周期阻滞,在 T47D 和 MCF-7 细胞中具有很强的细胞毒性。与未经处理的癌细胞相比,SB 处理的细胞还显示出 miR-20b 下调和 BCL2L11、PTEN 和 Caspase 9 mRNA 高表达。计算对接表明 SB/miR-20b 和 SB/Erbb2 之间存在很强的相互作用。可以得出结论,SB 通过上调 BCL2L11 和下调 miR-20b 表现出很强的抗肿瘤活性,可能通过靶向 PTEN 并与 Erbb2 相互作用,从而诱导细胞凋亡和细胞周期阻滞。