Telmisartan attenuates human glioblastoma cells proliferation and oncogenicity by inducing the lipid oxidation.
Telmisartan attenuates human glioblastoma cells proliferation and oncogenicity by inducing the lipid oxidation.
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DOI：
10.1111/ajco.13574
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发表时间：
2022-06
影响因子：
1.9
通讯作者：
Xue, Lixiang
中科院分区：
文献类型：
--
作者：
Wang, Yan;Zhang, Tengrui;Li, Chen;Guo, Jia;Xu, Baohui;Xue, Lixiang
胶质母细胞瘤（GBM）是最常见的原发性脑肿瘤之一，占恶性脑肿瘤的80%以上，5年相对生存率低于5%。近年来的研究表明，脂质代谢在GBM的发生发展中起着重要的作用。作为过氧化物酶体增殖物激活受体γ（PPAR-γ）激动剂，替米沙坦可改善脂质代谢，长期用于治疗高血压。它还被证明具有抗癌功能，如肺癌和黑色素瘤。使用Incucyte真实的实时活细胞成像系统评估替米沙坦对胶质瘤细胞系U87和U251增殖的影响。采用Transwell法和集落形成实验检测替米沙坦对GBM细胞系致瘤性的影响。采用Western blot和免疫荧光法检测替米沙坦对PPAR-γ和羟酰辅酶A脱氢酶α亚单位（HADHA）表达的影响。我们证明，替米沙坦以时间和剂量依赖性方式抑制两种胶质瘤细胞系U87和U251增殖，并将细胞周期阻滞在S期。我们进一步表明，替米沙坦降低GBM细胞系的致癌性。我们的数据表明，替米沙坦治疗显著增加了PPAR-γ表达水平，增强了脂质氧化，并上调了脂肪酸氧化关键酶HADHA的水平。替米沙坦可抑制人GBM细胞的增殖和致瘤性，同时还可增加人GBM细胞的脂质氧化。替米沙坦是一种PPAR-γ激动剂，通过诱导S期阻滞和增加脂质氧化引起的能量消耗，降低细胞增殖并抑制人GBM细胞系的致癌性。
Glioblastoma (GBM) is one of the most common primary brain tumors, which accounts up to 80% of malignant brain tumors and the 5‐year relative survival rate is below 5%. Recent studies showed that the lipid metabolism played an essential role in GBM development. As a peroxisome proliferators‐activated receptors γ (PPAR‐γ) agonist, telmisartan improves the lipid metabolism and has been used to treat hypertension for long time. It has also been shown to have anticancer function, such as in lung cancer and melanoma. Incucyte real‐time live cell imaging system was used to assess the effect of telmisartan on glioma cell lines U87 and U251 proliferation. Transwell assay and colony formation assay were conducted to detect the effect of telmisartan on oncogenicity of GBM cell lines. Western blot and immunofluorescence analysis were used to detect the effect of telmisartan on the expression of PPAR‐γ and hydroxyacyl‐coenzyme A dehydrogenase alpha subunit (HADHA). We demonstrate that telmisartan inhibits two glioma cell lines U87 and U251 proliferation in a time‐ and dose‐dependent manner, and arrests the cell cycle at S phase. We further show that telmisartan decreases the oncogenicity of GBM cell lines. Our data show that telmisartan treatment significantly increases the PPAR‐γ expression level, enhances the lipid oxidation, and upregulates the level of fatty acid oxidation key enzyme HADHA. Telmisartan inhibits the proliferation and oncogenicity while it also increases the lipid oxidation of human GBM cells. Telmisartan, a PPAR‐γ agonist, decreases the cell proliferation and inhibits the oncogenicity of human GBM cell lines by inducing S‐phase arrest and increasing the energy expenditure via lipid oxidation.
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Telmisartan通过阻断结肠癌细胞中ProHB-EGF C末端片段的核易位来抑制细胞增殖。
影响因子：
3.7
作者：
Ozeki K;Tanida S;Morimoto C;Inoue Y;Mizoshita T;Tsukamoto H;Shimura T;Kataoka H;Kamiya T;Nishiwaki E;Ishiguro H;Higashiyama S;Joh T
通讯作者：
Joh T
DOI：
10.3390/molecules19032862
发表时间：
2014-03-05
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Li J;Chen L;Yu P;Liu B;Zhu J;Yang Y
通讯作者：
Yang Y
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：
5.4
作者：
Grygiel-Górniak B
通讯作者：
Grygiel-Górniak B
影响因子：
5.5
作者：
Grahovac, Jelena;Srdic-Rajic, Tatjana;Radulovic, Sinisa
通讯作者：
Radulovic, Sinisa