Department of Biomedical Sciences and Clinical Research Center, College of Medicine, Inha University, Incheon, 400-712, Korea.
Arch Pharm Res. 2012 Mar;35(4):747-54. doi: 10.1007/s12272-012-0420-4. Epub 2012 May 3.
Hepatocellular carcinoma (HCC) is one of the most common malignancies, yet there have been no significant advances in effective therapeutics. In this study, HS-111 was synthesized as a novel thiazolamine derivative, N-(5-(2-chlorobenzyl) thiazole-2-yl) benzofuran-2-carboxamide, and its anticancer effect and mechanism were examined in human HCC cells. HS-111 strongly suppressed the growth of HCC cells in a dose-dependent manner. Also, apoptosis by HS-111 was identified by DAPI and TUNEL staining, and the increases of the cleaved caspase-3 were observed. In addition, HS-111 decreased protein expression of hypoxia-inducible factor (HIF-1α) and secretion of vascular endothelial growth factor (VEGF), and inhibited tube formation and the migration of human umbilical vein endothelial cells (HUVECs). These results showed that HS-111 not only inhibited cell growth and angiogenesis, but also induced apoptosis of human HCC cells. We suggest that HS-111 may be a potential candidate for chemotherapy against HCC.
肝细胞癌 (HCC) 是最常见的恶性肿瘤之一，但在有效的治疗方法方面尚无重大进展。在这项研究中，合成了一种新型噻唑胺衍生物 HS-111，即 N-(5-(2-氯苄基)噻唑-2-基)苯并呋喃-2-甲酰胺，并在人肝癌细胞中研究了其抗癌作用和机制。HS-111 强烈抑制 HCC 细胞的生长，呈剂量依赖性。此外，通过 DAPI 和 TUNEL 染色鉴定了 HS-111 诱导的细胞凋亡，并且观察到 cleaved caspase-3 的增加。此外，HS-111 降低了缺氧诱导因子 (HIF-1α) 的蛋白表达和血管内皮生长因子 (VEGF) 的分泌，并抑制了人脐静脉内皮细胞 (HUVEC) 的管形成和迁移。这些结果表明，HS-111 不仅抑制了细胞生长和血管生成，而且还诱导了人肝癌细胞的凋亡。我们认为 HS-111 可能是 HCC 化疗的潜在候选药物。
