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替米沙坦通过上调PPARγ和下调MMP-9表达来预防人卵巢癌细胞的增殖并促进其凋亡。

Telmisartan prevents proliferation and promotes apoptosis of human ovarian cancer cells through upregulating PPARγ and downregulating MMP‑9 expression.

作者信息

Pu Zhichen, Zhu Min, Kong Fandou

机构信息

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.

出版信息

Mol Med Rep. 2016 Jan;13(1):555-9. doi: 10.3892/mmr.2015.4512. Epub 2015 Nov 6.

DOI:10.3892/mmr.2015.4512
PMID:26548340
Abstract

The mortality rate of ovarian cancer is the highest of all gynecological malignancies. Telmisartan is a commonly used clinical angiotensin receptor blocker, which has antihypertensive, anti‑inflammatory and antithrombotic effects. In the present study, it was investigated whether telmisartan could exert anticancer effects on ovarian cancer cells through upregulating peroxisome proliferator‑activated receptor γ (PPARγ) and downregulating matrix metalloproteinase‑9 (MMP‑9) expression. A 3.3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was conducted to analyze the proliferation of HEY cells. A Caspase‑3 Activity Assay kit and an Annexin V‑fluorescein isothiocyanate/propidium iodide kit were used to analyze the apoptosis of HEY cells. In addition, a gelatin zymography assay and reverse trancription‑quantitative polymerase chain reaction were included to analyze the expression of PPARγ and MMP‑9 in HEY cells. The data showed that telmisartan could significantly decrease cell viability and induce the apoptosis of HEY cells in a time‑ and dose‑dependent manner. Furthermore, telmisartan could also dose‑dependently increase the expression of PPARγ and decrease the expression of MMP‑9 in HEY cells. In addition, downregulation of the expression of PPARγ by small interfering (si)RNA could reduce the effect of telmisartan on ovarian cancer cells and increase the expression of MMP‑9. In conclusion, the results indicated that telmisartan prevents proliferation and promotes apoptosis of human ovarian cancer cells by upregulating PPARγ and downregulating MMP‑9 expression.

摘要

卵巢癌的死亡率在所有妇科恶性肿瘤中是最高的。替米沙坦是一种常用的临床血管紧张素受体阻滞剂,具有降压、抗炎和抗血栓形成作用。在本研究中,研究了替米沙坦是否可通过上调过氧化物酶体增殖物激活受体γ(PPARγ)和下调基质金属蛋白酶9(MMP-9)的表达对卵巢癌细胞发挥抗癌作用。进行3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐试验以分析HEY细胞的增殖情况。使用半胱天冬酶-3活性检测试剂盒和膜联蛋白V-异硫氰酸荧光素/碘化丙啶试剂盒分析HEY细胞的凋亡情况。此外,还进行了明胶酶谱分析和逆转录-定量聚合酶链反应,以分析HEY细胞中PPARγ和MMP-9的表达。数据显示,替米沙坦可显著降低细胞活力,并以时间和剂量依赖性方式诱导HEY细胞凋亡。此外,替米沙坦还可剂量依赖性地增加HEY细胞中PPARγ的表达并降低MMP-9的表达。此外,小干扰(si)RNA下调PPARγ的表达可降低替米沙坦对卵巢癌细胞作用的效果,并增加MMP-9的表达。总之,结果表明替米沙坦通过上调PPARγ和下调MMP-9的表达来抑制人卵巢癌细胞的增殖并促进其凋亡。

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