研究动态
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ribociclib对MCF-7和MDA-MB-231细胞中miR-141和CDK4/6-USP51信号通路基因表达水平的影响。

The effect of ribociclib on the expression levels of miR-141 and CDK4/6-USP51 signaling pathway genes in MCF-7 and MDA-MB-231 cells.

发表日期:2024
作者: Shayeste Sadat Baghermanesh, Mahmood Barati, Arshad Hosseini
来源: GENES & DEVELOPMENT

摘要:

乳腺癌,尤其是三阴性乳腺癌患者的预后较差。这种疾病目前还没有有效的治疗方法。由于对化学疗法和放射疗法等传统疗法的抵抗,需要发现新的治疗策略来治疗这种疾病。 Ribociclib 是一种选择性 CDK4/6 抑制剂。大约 20% 的 HR 乳腺癌患者对 CDK4/6 抑制剂产生原发性耐药,超过 30% 的患者出现继发性耐药。由于大多数患者在 CDK4/6 抑制剂治疗期间会出现耐药性,因此治疗这种疾病变得更具挑战性。许多恶性肿瘤异常表达微小RNA(miR)-141,其参与多种细胞过程,包括耐药、增殖、上皮间质转化、迁移和侵袭。在本研究中,我们培养了MDA-MB-231和MCF- DMEM-F12 培养基中的 7 个细胞。通过MTT测定,我们测定了ribociclib对乳腺癌细胞的细胞毒作用,并测定了其IC50。然后,我们在两个时间点用 ribociclib 处理细胞:24 小时和 72 小时。之后,分离RNA并反转录为cDNA。最后,我们进行了 qRT-PCR 来评估 ribociclib 如何影响所需基因的表达水平。我们发现 ribociclib 可以以剂量和时间依赖性方式抑制细胞生长。我们检查了 4 个基因的 mRNA 表达。 ribociclib治疗后,CDK6和MYH10的mRNA表达下降(p < 0.01,p < 0.05)。 CDON mRNA 表达增加(p<0.05),但 ZEB1 mRNA 表达没有观察到显着变化。此外,miR-141 的 qRT-PCR 结果显示,用 ribociclib 处理 72 小时后,miR-141 的表达增加 (p<0.01)。版权所有:© 2024 Baghermanesh 等人。这是一篇根据知识共享署名许可条款分发的开放获取文章,允许在任何媒体上不受限制地使用、分发和复制,前提是注明原始作者和来源。
Patients with breast cancer, especially triple-negative breast cancer, have a poor prognosis. There is still no effective treatment for this disease. Due to resistance to traditional treatments such as chemotherapy and radiation therapy, there is a need to discover novel treatment strategies to treat this disease. Ribociclib is a selective CDK4/6 inhibitor. Approximately 20% of patients with HR+ breast cancer developed primary resistance to CDK4/6 inhibitors, and more than 30% experienced secondary resistance. Since most patients experience resistance during CDK4/6 inhibitor treatment, managing this disease is becoming more challenging. Many malignant tumors abnormally express microRNA (miR)-141, which participates in several cellular processes, including drug resistance, proliferation, epithelial-mesenchymal transition, migration, and invasion.In the present study, we cultured MDA-MB-231 and MCF-7 cells in DMEM-F12 medium. By performing MTT assay we determined the cytotoxic effects of ribociclib on breast cancer cells, as well as determining the IC50 of it. Then, we treated the cells with ribociclib at two time points: 24 h and 72 h. After that, RNA was isolated and reverse transcribed to cDNA. Finally, we performed qRT‒PCR to evaluate how ribociclib affects the expression level of desired genes.We found that ribociclib can inhibit cell growth in a dose- and time-dependent manner. We examined the mRNA expression of 4 genes. After ribociclib treatment, the mRNA expression of CDK6 and MYH10 decreased (p < 0.01, p < 0.05). The mRNA expression of CDON increased (p<0.05), but no significant changes were observed in ZEB1 mRNA expression. Furthermore, the qRT‒PCR results for miR-141 showed that the expression of miR-141 increased (p<0.01) after 72 h of treatment with ribociclib.Copyright: © 2024 Baghermanesh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.