Anticancer Effect of Emodin Combined with 5-fluorouracil on Human Gastric Carcinoma Cell Line MKN45 and its Molecular Mechanism

Abstract

AIM: The purpose of this study was to investigate the anticancer effect induced by and 5-fluorouracil (5-Fu) on human gastric carcinoma cell line MKN45, and to discuss its molecular mechanism. METHODS: Firstly, MTT assay was used to to assess the growth inhibiton effect of emodin and 5-Fu. Secondly, Flow cytometry was used to monitor the changes of cell cycle distribution and decipher the suppressive mechanisms of emodin on MKN45 cells. Thirdly, Acridine Orange staining was used to observe the nuclear morphological changes that occurred during emodin treatment. Finally, immunoblot analysis of proteins p53 and p21waf1 derived from emodin-treated MKN45 cells were analyzed to evaluate the mechanism of cell apoptosis induced by emodin. RESULTS: It showed that emodin induced cell death in a dose- and time-dependent manner and 10, 20 μg/mL of emodin combined with 10 mg/L 5-Fu significantly inhibited cell growth. Moreover, the G2/M phase blocking could be detected by flow cytometry. Apoptosis which correlated with concentration of emodin could also be observed by Acridine Orange staining. In addition, when exposured to emodin for 48 hours, a dose-dependent increase of proteins p53 and p21waf1 was observed, which indicated the potential mechanism of apoptosis induced by emodin. These studies suggested that emodin was a suitable and novel chemotherapeutic drug candidate for the treatment of human gastric carcinoma. CONCLUSION: These studies suggested that emodin was a suitable and novel chemotherapeutic drug candidate for the treatment of human gastric carcinoma.