Choi Hyeong Sim, Lee Kangwook, Kim Min Kyoung, Lee Kang Min, Shin Yong Cheol, Cho Sung-Gook, Ko Seong-Gyu
Department of Science in Korean Medicine, Graduate School, Kyung Hee University, 1 Hoegi, Seoul 130-701, Korea.
Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, 1 Hoegi, Seoul 130-701, Korea.
Oncotarget. 2016 Apr 19;7(16):21775-85. doi: 10.18632/oncotarget.7982.
Tumor growth requires a process called angiogenesis, a new blood vessel formation from pre-existing vessels, as newly formed vessels provide tumor cells with oxygen and nutrition. Danggui-Sayuk-Ga-Osuyu-Saenggang-Tang (DSGOST), one of traditional Chinese medicines, has been widely used in treatment of vessel diseases including Raynaud's syndrome in Northeast Asian countries including China, Japan and Korea. Therefore, we hypothesized that DSGOST might inhibit tumor growth by targeting newly formed vessels on the basis of its historical prescription. Here, we demonstrate that DSGOST inhibits tumor growth by inhibiting VEGF-induced angiogenesis. DSGOST inhibited VEGF-induced angiogenic abilities of endothelial cells in vitro and in vivo, which resulted from its inhibition of VEGF/VEGFR2 interaction. Furthermore, DSGOST attenuated pancreatic tumor growth in vivo by reducing angiogenic vessel numbers, while not affecting pancreatic tumor cell viability. Thus, our data conclude that DSGOST inhibits VEGF-induced tumor angiogenesis, suggesting a new indication for DSGOST in treatment of cancer.
肿瘤生长需要一个叫做血管生成的过程,即从已有的血管形成新的血管,因为新形成的血管为肿瘤细胞提供氧气和营养。当归芍药加术油芍药生姜汤(DSGOST)是一种中药,在中国、日本和韩国等东北亚国家已被广泛用于治疗包括雷诺氏综合征在内的血管疾病。因此,我们推测,基于其历史处方,DSGOST可能通过靶向新形成的血管来抑制肿瘤生长。在此,我们证明DSGOST通过抑制VEGF诱导的血管生成来抑制肿瘤生长。DSGOST在体外和体内均抑制VEGF诱导的内皮细胞血管生成能力,这是由于其抑制VEGF/VEGFR2相互作用所致。此外,DSGOST通过减少血管生成的血管数量来减弱体内胰腺肿瘤的生长,而不影响胰腺肿瘤细胞的活力。因此,我们的数据得出结论,DSGOST抑制VEGF诱导的肿瘤血管生成,提示DSGOST在癌症治疗中有新的应用前景。