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血管紧张素转换酶2/血管紧张素1-7/ Mas受体轴与血管紧张素转换酶/血管紧张素II/血管紧张素II 1型受体轴的调节影响了舍曲林对MCF-7乳腺癌细胞的抗癌特性。

Modulation of ACE2/Ang1-7/Mas and ACE/AngII/AT1 axes affects anticancer properties of sertraline in MCF-7 breast cancer cells.

作者信息

Fatehi Reihaneh, Nouraei Mohammad, Panahiyan Morteza, Rashedinia Marzieh, Firouzabadi Negar

机构信息

Department of Pharmacology & Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.

Student Research Comittee, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

Biochem Biophys Rep. 2024 May 23;38:101738. doi: 10.1016/j.bbrep.2024.101738. eCollection 2024 Jul.

DOI:10.1016/j.bbrep.2024.101738
PMID:38831897
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11145238/
Abstract

The renin-angiotensin system (RAS) is best known for playing a major role in maintaining the physiology of the cardiovascular system. Dysregulation of the RAS pathway has been proposed as a link to some malignancies and contributes to cancer metastasis. Breast cancer is considered as one of the leading causes of cancer death in women and its prevention remains yet a challenge. Elements of RAS are expressed in both normal breast tissue and cancerous cells, signifying the essential role of RAS in breast cancer pathology. Sertraline, a widely used antidepressant, has shown anti-proliferative properties on a variety of malignancies. This study aimed to investigate the effect of sertraline and its combination with agonists and antagonists of RAS (A779, Ang 1-7 and losartan) on viability of MCF-7 cells along with their effect on apoptosis and distribution of cell cycle. Our results indicated that sertraline, losartan and Ang 1-7 significantly decreased cell viability, induced apoptosis and cell cycle arrest. A779 blunted the effect of sertraline on cell viability, ROS generation and cell cycle arrest. Combination treatment of sertraline with losartan as well as Ang 1-7 caused a remarkable decline in cell viability. In conclusion, results of the present study support the anti-cancer properties of sertraline, losartan and Ang 1-7 via induction of apoptosis and cell cycle arrest.

摘要

肾素-血管紧张素系统（RAS）最为人所知的是在维持心血管系统生理功能方面发挥着重要作用。RAS通路的失调被认为是与某些恶性肿瘤相关的一个环节，并促进癌症转移。乳腺癌被认为是女性癌症死亡的主要原因之一，其预防仍然是一项挑战。RAS的成分在正常乳腺组织和癌细胞中均有表达，这表明RAS在乳腺癌病理过程中起着重要作用。舍曲林是一种广泛使用的抗抑郁药，已显示出对多种恶性肿瘤具有抗增殖特性。本研究旨在探讨舍曲林及其与RAS激动剂和拮抗剂（A779、血管紧张素1-7和氯沙坦）联合使用对MCF-7细胞活力的影响，以及它们对细胞凋亡和细胞周期分布的影响。我们的结果表明，舍曲林、氯沙坦和血管紧张素1-7显著降低细胞活力，诱导细胞凋亡和细胞周期停滞。A779减弱了舍曲林对细胞活力、活性氧生成和细胞周期停滞的影响。舍曲林与氯沙坦以及血管紧张素1-7联合治疗导致细胞活力显著下降。总之，本研究结果支持舍曲林、氯沙坦和血管紧张素1-7通过诱导细胞凋亡和细胞周期停滞而具有抗癌特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7841/11145238/cbd02377c344/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7841/11145238/e04aa17032b4/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7841/11145238/41e8a57d6b87/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7841/11145238/dcebc473ed59/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7841/11145238/532d1da8c904/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7841/11145238/b0727d639d94/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7841/11145238/cbd02377c344/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7841/11145238/e04aa17032b4/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7841/11145238/41e8a57d6b87/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7841/11145238/dcebc473ed59/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7841/11145238/532d1da8c904/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7841/11145238/b0727d639d94/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7841/11145238/cbd02377c344/gr6.jpg

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