title: Telmisartan prevents proliferation and promotes apoptosis of human ovarian cancer cells through upregulating PPARγ and downregulating MMP‑9 expression.
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.
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Zhichen
authors.initials: Z
authors.lastname: Pu
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Fandou
authors.initials: F
authors.lastname: Kong
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001562:Benzimidazoles / Q000737:chemistry / Q000494:pharmacology*; D001565:Benzoates / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000473:pathology*; D047495:PPAR gamma / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D000077333:Telmisartan; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D001562:Benzimidazoles; D001565:Benzoates; D047495:PPAR gamma; D034741:RNA, Small Interfering; D020780:Matrix Metalloproteinase 9; D000077333:Telmisartan