Exploring brusatol as a new anti-pancreatic cancer adjuvant: biological evaluation and mechanistic studies

摘要: // Zheng Lu 1, 2, 4 , Zheng-Quan Lai 1 Albert W.N. Leung Po Sing 3 Zhao-Shen Li 2 and Zhi-Xiu Lin School of Chinese Medicine, Faculty The University Hong Kong, Shatin, China Department Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, Biomedical Sciences, Liver Cirrhosis Diagnosis Treatment Center, Beijing 302 Beijing, Correspondence to: Lin, email: linzx@cuhk.edu.hk Keywords: pancreatic cancer, brusatol, gemcitabine, 5-fluorouracil, combination therapy Received: September 24, 2016     Accepted: April 17, 2017     Published: May 10, 2017 ABSTRACT Pancreatic cancer is highly resistant to chemotherapeutic agents known have a poor prognosis. development new therapeutic entities badly needed for this deadly malignancy. In study, we demonstrated the first time that natural quassinoid isolated from herbal medicine named Bruceae Fructus, possessed potent cytotoxic effect against different adenocarcinoma cell lines. Its anti-pancreatic was comparable first-line such as gemcitabine with more favorable safety profile. addition, brusatol showed synergistic anti-proliferative toward PANC-1 Capan-2 lines when combined or 5-fluorouracil. results flow cytometry suggested treatment 5-fluorouracil able cause cycle arrest at G2/M phase, accentuate apoptosis in cells. Moreover, deactivated gemcitabine/5-fluorouracil-induced NF-κB activation. Western blot analysis qRT-PCR significantly down-regulated expression vimentin Twist, markedly stimulated E-cadherin, key regulatory factors epithelial-mesenchymal transition process. Furthermore, reduced vivo tumor growth compared either gemcitabine/5-fluorouracil alone. Taken together, these amply compound, effects observed both vitro are associated suppression process, indicating promising adjunct current regimen.