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替米沙坦与多西他赛对人前列腺癌细胞和乳腺癌细胞活力及转移基因表达的联合作用

Combinatorial effects of telmisartan and docetaxel on cell viability and metastatic gene expression in human prostate and breast cancer cells.

作者信息

Khorsand Marjan, Mostafavi-Pour Zohreh, Razban Vahid, Khajeh Sahar, Zare Razieh

机构信息

Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

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

出版信息

Mol Biol Res Commun. 2022 Mar;11(1):11-20. doi: 10.22099/mbrc.2022.42638.1700.

Abstract

The epithelial-to-mesenchymal transition (EMT) is a unique process resulting in enhanced cell motility, invasiveness, and metastasis in cancer. The EMT is regulated by several transcription factors, including Snail and Slug, which exert crucial roles during cancer progression. We have studied the effects of Docetaxel as the first-line chemotherapy agent for prostate cancer, and Telmisartan as an anti-hypertensive drug on the expression level of Snail and Slug. In addition, the effects of Docetaxel, Telmisartan and their combination on cancer cell proliferation were investigated. The PC3, DU145, MDA-MB468, and HEK cell lines were used for this study. Quantitative RT-PCR analysis and MTT assay were used to study the expression of Snail and Slug level and cell proliferative assay, respectively. We found that a combination of Docetaxel + Telmisartan effectively inhibits the cell proliferation in cancerous cells in comparison with each drug alone (P<0.05). Furthermore, in these cell lines, Docetaxel, Telmisartan and their combination significantly diminished the expression level of Snail and Slug genes compared to control cells (P<0.001), however, in the HEK cell line, this effect was seen only in the combination group. Our data imply that Telmisartan and its combination with Docetaxel exert strong inhibitory effects on the expression level of Snail and Slug genes. Also, these drugs and their combination could inhibit cancer cell proliferation. In conclusion, the combination of Telmisartan and Docetaxel has the potential to suppress the metastasis of prostate and breast cancer cells.

摘要

上皮-间质转化(EMT)是一个独特的过程,会导致癌症细胞的运动性、侵袭性和转移性增强。EMT受多种转录因子调控,包括Snail和Slug,它们在癌症进展过程中发挥着关键作用。我们研究了多西他赛作为前列腺癌一线化疗药物以及替米沙坦作为抗高血压药物对Snail和Slug表达水平的影响。此外,还研究了多西他赛、替米沙坦及其组合对癌细胞增殖的影响。本研究使用了PC3、DU145、MDA-MB468和HEK细胞系。分别采用定量RT-PCR分析和MTT法研究Snail和Slug水平的表达以及细胞增殖实验。我们发现,与单独使用每种药物相比,多西他赛+替米沙坦联合用药能有效抑制癌细胞的增殖(P<0.05)。此外,在这些细胞系中,与对照细胞相比,多西他赛、替米沙坦及其组合显著降低了Snail和Slug基因的表达水平(P<0.001),然而,在HEK细胞系中,这种效应仅在联合用药组中可见。我们的数据表明,替米沙坦及其与多西他赛的组合对Snail和Slug基因的表达水平具有强烈的抑制作用。此外,这些药物及其组合可以抑制癌细胞的增殖。总之,替米沙坦和多西他赛的组合有可能抑制前列腺癌和乳腺癌细胞的转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/594e/9012430/20feb2a312d2/mbrc-11-11-g001.jpg

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