个人简介
Prof. Ling Zhao
Prof. Ling Zhao
Southwest Medical University, China
标题: Curcumin enhances the anticancer effect of 5-fluorouracil against gastric cancer
摘要: 
Background: 5-fluorouracil (5-FU) is one of the most commonly used first-line anticancer drugs to treat gastric cancer in clinical practice. However, severe adverse events such as gastrointestinal toxicity and bone marrow suppression limit its clinical application. Combination chemotherapy to combine two or more anticancer drugs with different mechanistic action is an effective anticancer strategy against gastric cancer. Therefore, we studied the anticancer effect of the combination of 5-FU with curcumin against gastric cancer MKN45 and AGS cells (normal gastric mucosal GES-1 cells as control) and associated molecular mechanisms. 
Methods: Cytotoxicity of 5-FU and curcumin alone or in combination was evaluated in MKN45, AGS and GES cells by MTT assay. The protein expressions of COX-2 and NF-κB were evaluated in MKN45 cells by Western blotting analysis. In addition, antitumor activity of 5-FU and curcumin alone or in combination was evaluated in nude mice bearing MKN45 tumor xenografts in vivo.
Results: The combination of 5-FU and curcumin (2:1, mol/mol) showed 2.2-, 3.5-fold and 2.3-, 3.9-fold enhanced cytotoxic effect compared to 5-FU or curcumin alone and generated synergistic effect at the concentration of 5-FU (>4.09 and >5.71 μmol/l) and curcumin (>2.05 and > 2.86 μmol/l) in MKN45 cells for 48 h and 72 h exposures, respectively. The combination of 5-FU and curcumin also potentiated cytotoxicity in AGS cells compared to 5-FU or curcumin alone but the effect was moderate. However, the cytotoxicity of 5-FU and curcumin alone or in combination was much less in GES-1 cells. Furthermore, the protein expressions of COX-2 and NF-κB in MKN45 cells were decreased by 44.79% and 37.67%, 47.17% and 48.21%, 60.21% and 62.44%, respectively, after treatment of curcumin (25 μmol/l) and 5-FU (50 μmol/l) alone or in combination for 48 h. Curcumin also enhanced the anticancer activity of 5-FU without increasing toxicity in nude mice bearing MKN45 tumor xenografts in vivo.
Conclusions: Curcumin enhances the anticancer effect of 5-FU against gastric cancer in vitro and in vivo. The possible molecular mechanism may be, at least in part, related to down-regulation of COX-2 and NF-κB pathways. 

Keywords: 5-fluorouracil, curcumin, gastric cancer, MKN45 cell, COX-2, NF-κB
简介: 
Ling Zhao, 39 years old, PhD,Professor of Pharmacy,Vice Dean of School of Pharmacy of Southwest Medical University. Outstanding experts with outstanding contributions in Sichuan Province. Candidates for academic and technical leaders in Sichuan Province. Winners of Distinguished Young Scholars of Sichuan Province. Academic and technological leaders in Luzhou City. Invited members of Luzhou Municipal Government Advisory Committee on policy making. Served as an editorial board or reviewer for the following journals: J Biochem Mole Biolo Res; Journal of Southwest Medical University; J Biomed; Int J Nanomed; Scientific Reports ,Carbohyd Polym; Drug Design, Development and Therapy; Drug Dev Ind Pharm; Drug Deliv; Mat Sci Eng B-Solid; J Liposome Res; Biomedical Chromatography; Pharm Dev Technol; Iran Polym J; Current Pharmaceutical Analysis. The main research areas: Design and evaluation of novel tumor targeting drug delivery systems based on lipid and nanoparticles, novel nana-drug delivery systems for improving the solubility and bioavailability of poorly soluble drugs; the structural modification and mechanism of action of effective monomer of Chinese Medicine and new compound prescription of Traditional Chinese Medicine for cancer therapeutics. I have maintained strong interdisciplinary interactions with physician scientists in areas of breast cancer, hepatocellular carcinoma and lung cancer. In addition, I work closely with the pharmaceutical and biotechnology industries. My project recently has been licensed to Luzhou Qinpai Company Ltd. (Luzhou, China). Grant support: National Natural Science Foundation of China, the Science and Technology Fund of for Distinguished Young Scholars of Sichuan Province, etc. As the first or communication author published 25 SCI papers, 5 Patents; “Innovation and application of key technologies of controlled release and targeted drug delivery system”, The Second Prize of Sichuan Science and Technology Improvement Prize as the first accomplisher. “Research and application of drug delivery system and pharmacokinetics”, the First Prize of Science and Technology Improvement Prize in Luzhou as the first accomplisher, etc.