Thioridazine inhibits angiogenesis and tumor growth by targeting the VEGFR-2/PI3K/mTOR pathway in ovarian cancer xenografts.
Thioridazine inhibits angiogenesis and tumor growth by targeting the VEGFR-2/PI3K/mTOR pathway in ovarian cancer xenografts.
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DOI：
10.18632/oncotarget.2063
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发表时间：
2014-07-15
期刊：
影响因子：
--
通讯作者：
Rho SB
中科院分区：
文献类型：
--
作者：
Park MS;Dong SM;Kim BR;Seo SH;Kang S;Lee EJ;Lee SH;Rho SB
硫利达嗪是吩噻嗪家族的一员，是一种强效抗焦虑和抗精神病药物。它还可以抑制几种类型的肿瘤在体外的生长。在本研究中，我们评估了硫利达嗪在体内的直接抗肿瘤和抗血管生成作用。将硫利达嗪注射到裸鼠的人卵巢肿瘤异种移植物中显著抑制肿瘤生长约5倍，并且还减少肿瘤血管。此外，在卵巢肿瘤进展期间，硫利达嗪通过血管内皮生长因子受体2（VEGFR-2）抑制磷脂酰肌醇-3 '-激酶（PI 3 K）下游信号分子（包括Akt、磷酸肌醇依赖性蛋白激酶1（PDK 1）和哺乳动物雷帕霉素靶蛋白（mTOR））的磷酸化。这些结果为硫利达嗪通过抑制VEGFR-2/PI 3 K/mTOR信号转导调节内皮细胞功能和随后的血管生成提供了令人信服的证据。总的来说，这些结果强烈表明，硫利达嗪可能是一种新的抗肿瘤和抗血管生成剂用于卵巢癌。
Thioridazine, a member of the phenothiazine family, is a powerful anti-anxiety and anti-psychotic drug. It can also suppress the growth of several types of tumor in vitro. In the current study, we evaluated the direct anti-tumor and anti-angiogenic effects of thioridazine in vivo. The injection of thioridazine into human ovarian tumor xenografts in nude mice significantly inhibited tumor growth by ~fivefold, and also decreased tumor vascularity. In addition, thioridazine inhibited the phosphorylation of the signaling molecules downstream of phosphatidylinositol-3’-kinase (PI3K), including Akt, phosphoinositide-dependent protein kinase 1 (PDK1), and mammalian target of rapamycin (mTOR), during ovarian tumor progression via vascular endothelial growth factor receptor 2 (VEGFR-2). These results provide convincing evidence that thioridazine regulates endothelial cell function and subsequent angiogenesis by inhibiting VEGFR-2/PI3K/mTOR signal transduction. Collectively, these results strongly suggest that thioridazine might be a novel anti-tumor and anti-angiogenic agent for use in ovarian cancer.
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影响因子：
2.7
作者：
Pantazaki, AA;Lialiaris, TS
通讯作者：
Lialiaris, TS
影响因子：
3.1
作者：
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影响因子：
5.6
作者：
Xia, Chang;Meng, Qiao;Jiang, Bing-Hua
通讯作者：
Jiang, Bing-Hua
影响因子：
64.8
作者：
Risau, W
通讯作者：
Risau, W
肿瘤发生和血管生成中的 PI3K/PTEN 信号传导。
DOI：
10.1016/j.bbapap.2007.09.008
发表时间：
2008-01-01
影响因子：
3.2
作者：
Jiang, Bing-Hua;Liu, Ling-Zhi
通讯作者：
Liu, Ling-Zhi