Miyake Tatsuya, Kumasawa Keiichi, Sato Noriko, Takiuchi Tsuyoshi, Nakamura Hitomi, Kimura Tadashi
Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita 565-0871, Japan.
Sci Rep. 2016 Apr 22;6:24853. doi: 10.1038/srep24853.
Soluble Vascular Endothelial Growth Factor Receptor 1 (sVEGFR1/sFLT1) is an angiogenesis inhibitor that competes with angiogenic factors such as VEGF and Placental Growth Factor (PlGF). Imbalances of VEGF and sFLT1 levels can cause pathological conditions such as tumour growth or preeclampsia. We observed direct damage caused by sFLT1 in tumour cells. We exposed several kinds of cells derived from ovarian and colorectal cancers as well as HEK293T cells to sFLT1 in two ways, transfection and exogenous application. The cell morphology and an LDH assay revealed cytotoxicity. Additional experiments were performed to clarify how sFLT1 injured cells. In this study, non-apoptotic cell damage was found to be induced by sFLT1. Moreover, sFLT1 showed an anti-tumour effect in a mouse model of ovarian cancer. Our results suggest that sFLT1 has potential as a cancer therapeutic candidate.
可溶性血管内皮生长因子受体1(sVEGFR1/sFLT1)是一种血管生成抑制剂,可与血管生成因子如血管内皮生长因子(VEGF)和胎盘生长因子(PlGF)竞争。VEGF和sFLT1水平的失衡可导致肿瘤生长或先兆子痫等病理状况。我们观察到sFLT1对肿瘤细胞造成的直接损伤。我们通过转染和外源应用两种方式,将几种源自卵巢癌和结直肠癌的细胞以及人胚肾293T细胞暴露于sFLT1中。细胞形态和乳酸脱氢酶(LDH)检测显示出细胞毒性。我们进行了额外的实验以阐明sFLT1如何损伤细胞。在本研究中,发现sFLT1可诱导非凋亡性细胞损伤。此外,sFLT1在卵巢癌小鼠模型中显示出抗肿瘤作用。我们的结果表明,sFLT1有潜力成为癌症治疗候选药物。