Li Wei, Zhang Hongxiu, Nie Mingxiu, Tian Yanlei, Chen Xu, Chen Ceshi, Chen Haijun, Liu Rong
Department of Urology of the First People's Hospital of Yunnan Province, Kunming 650032, China.
Medical College of Kunming University of Science and Technology, Kunming 650032, China.
Acta Biochim Biophys Sin (Shanghai). 2017 Apr 1;49(4):367-373. doi: 10.1093/abbs/gmx012.
Advanced renal cell carcinoma and triple negative breast cancer (TNBC) are malignancies without effective therapeutics currently. Ursolic acid (UA) has been previously reported to have anti-cancer effects in multiple solid tumors. In order to develop more potent anti-cancer reagents, FZU-03,010 based on the chemical structure of UA were synthesized. The results demonstrated that, compared with UA, FZU-03,010 could suppress renal cancer cell 786-0 and TNBC cell HCC1806 cell viability more potently. Furthermore, FZU-03,010 could induce G1 cell cycle arrest and cell apoptosis more efficiently than UA. FZU-03,010 could also inhibit signal transducer and activator of transcription 3 activation, induce the expression of cell cycle-dependent kinase inhibitors (p21 and p27) and promote cell apoptosis. In conclusion, our results suggest that the UA derivative FZU-03,010 is more potent in inhibiting cancer cell survival, and FZU-03,010 has the potential to be developed as a therapeutic for renal cell cancers and TNBCs.
晚期肾细胞癌和三阴性乳腺癌（TNBC）目前是没有有效治疗方法的恶性肿瘤。熊果酸（UA）此前已被报道在多种实体瘤中具有抗癌作用。为了开发更有效的抗癌试剂，基于UA的化学结构合成了FZU-03010。结果表明，与UA相比，FZU-03010能更有效地抑制肾癌细胞786-0和TNBC细胞HCC1806的细胞活力。此外，FZU-03010比UA能更有效地诱导G1期细胞周期阻滞和细胞凋亡。FZU-03010还能抑制信号转导和转录激活因子3的激活，诱导细胞周期依赖性激酶抑制剂（p21和p27）的表达并促进细胞凋亡。总之，我们的结果表明，UA衍生物FZU-03010在抑制癌细胞存活方面更有效，并且FZU-03010有潜力被开发成为肾细胞癌和TNBC的一种治疗药物。
