Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Bone and Joint Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
J Cell Mol Med. 2022 Apr;26(8):2392-2403. doi: 10.1111/jcmm.17259. Epub 2022 Feb 27.
This study aimed to investigate if Telmisartan as a novel N-cadherin antagonist, can overcome cell migration of cancer cells. We investigated the mechanism and influence of Docetaxel and Telmisartan (as an analogous to ADH-1, which is a well-known N-cadherin antagonist) on cancer cells. The effect of ADH-1 and Telmisartan on cell attachment in PC3, DU145, MDA-MB-468 cell lines using recombinant human N-cadherin was studied. Cell viability assay was performed to examine the anti-proliferative effects of Telmisartan, ADH-1 and Docetaxel. Migration was examined via wound healing assay, and apoptosis was determined by flow cytometry. The expression of AKT-1 as a downstream gene of N-cadherin signalling pathway was assayed by real-time PCR. Treatment of PC3, MDA-MB-468 and DU145 cells with Telmisartan (0.1 µM) and ADH-1 (40 µM) resulted in 50%, 58% and approximately 20% reduction in cell attachment to N-cadherin coated plate respectively. It shows reduction of cell attachment in PC3 and MDA-MB-468 cell lines appeared to be more sensitive than that of DU145 cells to the Telmisartan and ADH-1 treatments. Telmisartan (0.1 µM) and Docetaxel (0.01 nM) significantly reduced cell migration in PC3 and MDA-MB-468 cell lines compared with the control group. Using Real-time PCR, we found that Telmisartan, Docetaxel and ADH-1 had significant influence on the AKT-1 mRNA level. The results of the current study for the first time suggest that, Telmisartan, exerts anti-proliferation and anti-migration effects by targeting antagonistically N-cadherin. Also, these data suggest that Telmisartan as a less expensive alternative to ADH-1 could potentiate Docetaxel anticancer effects.
本研究旨在探讨替米沙坦作为一种新型 N-钙黏蛋白拮抗剂是否能抑制癌细胞的迁移。我们研究了多西紫杉醇和替米沙坦（作为 ADH-1 的类似物，ADH-1 是一种众所周知的 N-钙黏蛋白拮抗剂）对癌细胞的作用机制和影响。使用重组人 N-钙黏蛋白研究 ADH-1 和替米沙坦对 PC3、DU145、MDA-MB-468 细胞系细胞黏附的影响。通过细胞活力测定法检测替米沙坦、ADH-1 和多西紫杉醇的抗增殖作用。通过划痕愈合试验检测迁移，通过流式细胞术检测凋亡。通过实时 PCR 测定 AKT-1 作为 N-钙黏蛋白信号通路下游基因的表达。替米沙坦（0.1μM）和 ADH-1（40μM）处理 PC3、MDA-MB-468 和 DU145 细胞导致细胞与涂覆有 N-钙黏蛋白的平板的黏附分别减少 50%、58%和大约 20%。结果表明，与 DU145 细胞相比，替米沙坦和 ADH-1 处理降低了 PC3 和 MDA-MB-468 细胞系的细胞黏附，且效果更为明显。与对照组相比，替米沙坦（0.1μM）和多西紫杉醇（0.01nM）显著降低了 PC3 和 MDA-MB-468 细胞系的细胞迁移。通过实时 PCR，我们发现替米沙坦、多西紫杉醇和 ADH-1 对 AKT-1 mRNA 水平有显著影响。本研究首次表明，替米沙坦通过拮抗 N-钙黏蛋白发挥抗增殖和抗迁移作用。此外，这些数据表明，替米沙坦作为 ADH-1 的一种更便宜的替代品，可以增强多西紫杉醇的抗癌作用。
