title: Telmisartan exerts anti-tumor effects by activating peroxisome proliferator-activated receptor-γ in human lung adenocarcinoma A549 cells.
abstract: Telmisartan, a member of the angiotensin II type 1 receptor blockers, is usually used for cardiovascular diseases. Recent studies have showed that telmisartan has the property of PPARγ activation. Meanwhile, PPARγ is essential for tumor proliferation, invasion and metastasis. In this work we explore whether telmisartan could exert anti-tumor effects through PPARγ activation in A549 cells. MTT and trypan blue exclusion assays were included to determine the survival rates and cell viabilities. RT-PCR and western blotting were used to analyze the expression of ICAM-1, MMP-9 and PPARγ. DNA binding activity of PPARγ was evaluated by EMSA. Our data showed that the survival rates and cell viabilities of A549 cells were all reduced by telmisartan in a time- and concentration-dependent manner. Meanwhile, our results also demonstrated that telmisartan dose-dependently inhibited the expression of ICAM-1 and MMP-9. Moreover, the cytotoxic and anti-proliferative effects, ICAM-1 and MMP-9 inhibitive properties of telmisartan were totally blunted by the PPARγ antagonist GW9662. Our findings also showed that the expression of PPARγ was up-regulated by telmisartan in a dose dependent manner. And, the EMSA results also figured out that DNA binding activity of PPARγ was dose-dependently increased by telmisartan. Additionally, our data also revealed that telmisartan-induced PPARγ activation was abrogated by GW9662. Taken together, our results indicated that telmisartan inhibited the expression of ICAM-1 and MMP-9 in A549 cells, very likely through the up-regulation of PPARγ synthesis.
authors.affiliation: Thoracic Oncology Department, Sichuan Cancer Hospital, Chengdu, Sichuan 610041, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Oncology Department, Sichuan Provincial Hospital and Sichuan Academy of Medical Science, Chengdu, Sichuan 610072, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Thoracic Oncology Department, Sichuan Cancer Hospital, Chengdu, Sichuan 610041, China. yuping20101215@163.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Yu
authors.affiliation: Thoracic Oncology Department, Sichuan Cancer Hospital, Chengdu, Sichuan 610041, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Thoracic Oncology Department, Sichuan Cancer Hospital, Chengdu, Sichuan 610041, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Thoracic Oncology Department, Sichuan Cancer Hospital, Chengdu, Sichuan 610041, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D000077192:Adenocarcinoma of Lung; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000819:agonists; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000077333:Telmisartan
chemical_list: D000970:Antineoplastic Agents; D001562:Benzimidazoles; D001565:Benzoates; D004268:DNA-Binding Proteins; D047495:PPAR gamma; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D020780:Matrix Metalloproteinase 9; D000077333:Telmisartan