Abstract:
Objective This study was designed to explore the effects and mechanisms of raltitrexed on the growth of the human gastric cancer cell line (MGC-803) transplanted in nude mice.
Methods Models of MGC-803 xenograft transplanted in nude mice were established. Body weight, mental state, food, and stool of the nude mice were closely monitored, and the inhibitory action in the tumors was evaluated after drug intervention. Distribution and apoptosis of the tumor cells were examined through flow cytometric assay. P53 mRNA and protein expression levels were determined through reverse transcription-polymerase chain reaction and Western blot analysis. Changes among the three groups were compared.
Results Body weights and tumor volumes of the nude mice were lower in the raltitrexed and 5-fluorouracil (5-Fu) groups than those in the control group. Tumor inhibition ratios were 49.02% and 45.75% in the raltitrexed and 5-Fu groups, respectively. In the G0/G1 stage, the number of cells decreased in the raltitrexed and 5-Fu groups. Significant differences were found between the experimental and control groups (P < 0.01). In the S stage, the number of cells increased in the raltitrexed and 5-Fu groups, with significant differences from the control group (P < 0.01). P53 mRNA and protein expression levels in the raltitrexed and 5-Fu groups were significantly higher than those in the control group (P < 0.01), but no significant differences were found between the raltitrexed and 5-Fu groups (P>0.05).
Conclusion Raltitrexed can inhibit the growth of MGC-803 xenograft transplanted in nude mice and shows inhibitory effect similar to that of 5-Fu. Raltitrexed can induce the S-phase block of the cell cycle and cell apoptosis in the MGC-803 xenografts in the nude mice. This drug may exhibit an antitumor effect by upregulating the p53 mRNA and protein expression levels.