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New strategy for breast cancer treatment: Neoribocic inhibits tumor proliferation through cell cycle blockade

ABSTRACT: As one of the most common malignant tumors in the world, breast cancer is still a major challenge to human health despite the continuous improvement of treatment methods. Therefore, it is of great clinical significance to develop new anti-breast cancer drugs to improve the therapeutic effect. As a CDK4/6 inhibitor, Ribociclib has shown potential in breast cancer treatment. Based on this, we designed and synthesized a new type of ribocyclib derivative Neoribocic, and deeply studied its role mechanism in breast cancer. Research results show that Neoribocic can significantly inhibit the proliferation, migration and invasion ability of breast cancer cells in in vitro experiments, and show excellent anti-tumor activity. By analyzing MDA-MB-231 cells treated with Neoribocic through RNA sequencing (RNA-Seq), we found that Neoribocic may block the progression of breast cancer cells in the G2/M stage by activating the p53 signaling pathway, thus exerting their anti-tumor effect. . In addition, in vivo experiments further confirm that Neoribocic can not only effectively inhibit tumor growth, but also significantly inhibit the angiogenesis in the chicken embryonic cyst membrane, suggesting that it may have an anti-angiogenesis effect.

ORGANISM(S): Homo sapiens

PROVIDER: GSE294436 | GEO | 2025/04/11

REPOSITORIES: GEO

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Project description:Background: Docosahexaenoic acid (DHA) is a natural compound with anticancer and anti-angiogenesis activity that is currently under investigation as both a preventative agent and an adjuvant to breast cancer therapy. However, the precise mechanisms of DHA’s anticancer activities are unclear. It is understood that the intercommunication between cancer cells and their microenvironment is essential to tumor angiogenesis. Exosomes are extracellular vesicles that are important mediators of intercellular communication and play a role in promoting angiogenesis. However, very little is known about the contribution of breast cancer exosomes to tumor angiogenesis or whether exosomes can mediate DHA’s anticancer action. Results: Exosomes were collected from MCF7 and MDA-MB-231 breast cancer cells after treatment with DHA. We observed an increase in exosome secretion and exosome microRNA contents from the DHA-treated cells. The expression of 83 microRNAs in the MCF7 exosomes was altered by DHA (>2-fold). The most abundant exosome microRNAs (let-7a, miR-23b, miR-27a/b, miR-21, let-7, and miR-320b) are known to have anti-cancer and/or anti-angiogenic activity. These microRNAs were also increased by DHA treatment in the exosomes from other breast cancer lines (MDA-MB-231, ZR751 and BT20), but not in exosomes from normal breast cells (MCF10A). When DHA-treated MCF7 cells were co-cultured with or their exosomes were directly applied to endothelial cell cultures, we observed an increase in the expression of these microRNAs in the endothelial cells. Furthermore, overexpression of miR-23b and miR-320b in endothelial cells decreased the expression of their pro-angiogenic target genes (PLAU, AMOTL1, NRP1 and ETS2) and significantly inhibited tube formation by endothelial cells, suggesting that the microRNAs transferred by exosomes mediate DHA’s anti-angiogenic action. These effects could be reversed by knockdown of the Rab GTPase, Rab27A, which controls exosome release. Conclusions: We conclude that DHA alters breast cancer exosome secretion and microRNA contents, which leads to the inhibition of angiogenesis. Our data demonstrate that breast cancer exosome signaling can be targeted to inhibit tumor angiogenesis and provide new insight into DHA’s anticancer action, further supporting its use in cancer therapy. Examination of small RNA populations in MCF7 cells and exosomes after DHA treatment.

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New strategy for breast cancer treatment: Neoribocic inhibits tumor proliferation through cell cycle blockade

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