Telmisartan exerts anti-tumor effects by activating peroxisome proliferator-activated receptor-γ in human lung adenocarcinoma A549 cells.
Telmisartan exerts anti-tumor effects by activating peroxisome proliferator-activated receptor-γ in human lung adenocarcinoma A549 cells.
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DOI：
10.3390/molecules19032862
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发表时间：
2014-03-05
期刊：
影响因子：
--
通讯作者：
Yang Y
中科院分区：
文献类型：
--
作者：
Li J;Chen L;Yu P;Liu B;Zhu J;Yang Y
替米沙坦是血管紧张素 II 1 型受体阻滞剂的成员，通常用于治疗心血管疾病。最近的研究表明，替米沙坦具有激活PPARγ的特性。同时，PPARγ对于肿瘤的增殖、侵袭和转移至关重要。在这项工作中，我们探讨替米沙坦是否可以通过激活 A549 细胞中的 PPARγ 发挥抗肿瘤作用。 MTT 和台盼蓝排除试验被用来确定存活率和细胞活力。采用RT-PCR和蛋白质印迹法分析ICAM-1、MMP-9和PPARγ的表达。通过EMSA评估PPARγ的DNA结合活性。我们的数据显示，替米沙坦以时间和浓度依赖性方式降低 A549 细胞的存活率和细胞活力。同时，我们的结果还表明，替米沙坦剂量依赖性地抑制ICAM-1和MMP-9的表达。此外，替米沙坦的细胞毒性和抗增殖作用、ICAM-1 和 MMP-9 抑制特性被 PPARγ 拮抗剂 GW9662 完全削弱。我们的研究结果还表明，替米沙坦以剂量依赖性方式上调 PPARγ 的表达。而且，EMSA 结果还表明，替米沙坦呈剂量依赖性地增加 PPARγ 的 DNA 结合活性。此外，我们的数据还显示，替米沙坦诱导的 PPARγ 激活被 GW9662 消除。综上所述，我们的结果表明，替米沙坦抑制 A549 细胞中 ICAM-1 和 MMP-9 的表达，很可能是通过上调 PPARγ 合成来实现的。
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.
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DOI：
10.1161/atvbaha.112.300985
发表时间：
2013-08
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Siragusa M;Sessa WC
通讯作者：
Sessa WC
影响因子：
6.7
作者：
Traub S;Nikonova A;Carruthers A;Dunmore R;Vousden KA;Gogsadze L;Hao W;Zhu Q;Bernard K;Zhu J;Dymond M;McLean GR;Walton RP;Glanville N;Humbles A;Khaitov M;Wells T;Kolbeck R;Leishman AJ;Sleeman MA;Bartlett NW;Johnston SL
通讯作者：
Johnston SL
影响因子：
7.3
作者：
Girnun, Geoffrey D.
通讯作者：
Girnun, Geoffrey D.
影响因子：
11.5
作者：
Lin, Yi-Chu;Shun, Chia-Tung;Chen, Ching-Chow
通讯作者：
Chen, Ching-Chow
DOI：
10.2741/4021
发表时间：
2012-01-01
期刊：
Frontiers in bioscience (Landmark edition)
影响因子：
--
作者：
Robbins GT;Nie D
通讯作者：
Nie D