氯沙坦
癌症研究
血管紧张素II
细胞生长
癌基因
受体
CTGF公司
细胞凋亡
细胞
化学
药理学
医学
细胞周期
内分泌学
癌症
内科学
生长因子
生物化学
作者
Soichiro Saikawa,Kosuke Kaji,Norihisa Nishimura,Kazuhiko Seki,Shinya Sato,Keisuke Nakanishi,Koh Kitagawa,Hideto Kawaratani,Mitsuteru Kitade,Kyoji Moriya,Tadashi Namisaki,Akira Mitoro,Hitoshi Yoshiji
标识
DOI:10.1016/j.canlet.2018.07.021
摘要
Cholangiocarcinoma (CCA) is a destructive malignancy with limited responsiveness to conventional chemotherapy. Although angiotensin receptor blockers (ARBs) have gained attention for their potential anticancer activity, little is known about their effects on CCA. The transcriptional co-activator, Yes-associated protein (YAP) is a critical oncogene in several cancers, including CCA. Following recent evidence showing that YAP is regulated by angiotensin II (AT-II), we investigated the effects of an ARB, losartan, on two human CCA cell lines (KKU-M213 and HuCCT-1) with regards to YAP oncogenic regulation. Losartan suppressed AT-II-induced CCA cell proliferation in a dose-dependent manner, induced apoptosis, decreased YAP (Ser127), and downregulated the YAP target genes CTGF, CYR61, ANKRD1, and MFAP5. However, losartan did not affect epithelial–mesenchymal transition, differentiation, or stemness in the CCA cells. Xenograft tumor growth assay showed that oral administration of a low clinical dose of losartan considerably reduced subcutaneous tumor burden and attenuated intratumor vascularization in CCA cell-derived xenograft tumors in BALB/c nude mice. These results indicate that ARB therapy could serve as a potential novel strategy for CCA treatment.
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