Effect Of Telmisartan On Cell Growth And Proliferation And Expression Of VEGF And MMP-2 In Human Non-small Cell Lung Cancer(NSCLC) Cell Line A549

Background and Purpose: Telmisartan, a member of the angiotensin II type 1 receptor(AT1R) blockers, plays an important role in tumor cell growth, proliferation, apoptosis, invasion and metastasis. This study intends to further investigate the effects of telmisartan on human non-small cell lung cancer(NSCLC) A549 cells in vitro and its possible mechanism. Methods: The expression levels of AT1 R in A549 cells before and after telmisartan treatment via RT-PCR and Western blot analysis, the cytotoxicity of telmisartan on the growth and proliferation of A549 cells in vitro were determined by MTT assay. The effects of telmisartan on cell cycle phase distribution and cell apoptosis in A549 cells was assessed by flow cytometry with PI staining and Annexin V-FITC/PI double staining, respectively. Furthermore, the secreted VEGF proteins were quantitatively detected using a commercial ELISA kit, the activity of matrix metalloproteinase-2(MMP-2) was analysed by gelatin zymography, and the expression levels of VEGF mRNA and MMP-2 mRNA was detected by RT-PCR. Results: A549 cells have the expression of AT1 R, and telmisartan(10-6 M, 10-5 M, and 10-4 M) can inhibit the growth and proliferation of A549 cells in a time- and concentration-dependent manner. In addition, telmisartan also can antagonize cell growth and proliferation stimulated by angiotensi-II(Ang-II). After treated with telmisartan for 48 h, the expression level of AT1 R in A549 cells was downregulated, cell cycle was arrested at the G1 phase and cell apoptosis was significantly increased as the concentration of telmisartan was increased. On the other hand, the quantities of secreted VEGF protein by A549 cells and the activity of MMP-2 were gradually decreased as the concentration of telmisartan was increased, and the expression of VEGF mRNA and MMP-2 mRNA decreased to the lowest levels when the concentration of telmisartan was 10-4 M. Conclusion: Telmisartan inhibited the growth and proliferation of A549 cells in a time- and concentration-dependent manner. Its possible mechanism included: after combined with AT1 R in A549 cells, telmisartan activated intracellular signal transduction pathways, and subsequently induced cell cycle arrest and cell apoptosis. Besides, telmisartan attenuated the abilities of cell growth, proliferation, migration and invasion in A549 cells possibly through downregulating the expression levels of VEGF and MMP-2.