关键词: 　5-FU, 胃癌, &Delta, 133p53, MDM2, cyclin G1

Abstract:
Background and purpose: Δ133p53 can promote tumor cell growth, but the exact mechanism is not clear. This study was aimed to observe the expression and significant of the p53 isoforms Δ133p53 and p53 gene downstream molecules MDM2 and cyclin G1 genes by 5-FU-MKN45 gastric cancer cell line model. Methods: After using different concentrations of 5-FU (50 μg/mL, 100 μg/mL) to human gastric cancer cell line MKN45, inhibition rate should be detected by MTT assay, the changes of Δ133p53 mRNA, MDM2 mRNA and cyclin G1 mRNA expressing were detected by reverse transcription-polymerase chain reaction (RT-PCR). Differences between these groups were analyzed by ANOVA, comparisons within groups were analyzed by t-test, bivariate correlation was analyzed by Pearson linear correlation. Results: MTT results showed that with the increased concentration of 5-FU and the extension of time, the cell inhibition rates increased gradually. The inhibition rates of 50 μg/mL 5-FU were 41.10%, 54.79% and 68.48%, for culturing 24, 48 and 72 hours. There were statistically significant differences between the groups(F=45.52, P=0.00). The inhibition rates of 100 μg/mL 5-FU were 69.53%, 78.21% and 86.92%, for culturing 24, 48 and 72 hours. There were statistically significant differences between the groups(F=85.58，P=0.00). The inhibition rates of 50 and 100 μg/mL were 41.10% and 69.53%, for culturing 24 hours. There were statistically significant differences between the groups(F=51.29, P=0.00). The inhibition rates of 50 and 100 μg/mL were 54.79% and 78.21%, for culturing 48 hours. There were statistically significant differences between the groups(F=51.29, P=0.00). The inhibition rates of 50 and 100 μg/mL were 68.48% and 86.82%, for culturing 72 hours. There were statistically significant differences between the groups(104.91, P=0.00). RT-PCR results showed that with the increase of the concentration of 5-FU, the Δ133p53 mRNA, MDM2 mRNA and cyclin G1 mRNA expression gradually declined in gastric cancer cell line MKN45 cells, and there were statistically significant differences between the groups(F=738.532, 1 396.607, 2 785.56，P=0.00). Correlation analysis showed that the expressions of Δ133p53 mRNA and MDM2 mRNA in gastric cancer were positively correlated (r=0.871, P=0.01), while the expression of cyclin G1 mRNA and p53 mRNA had no obvious relevance (P=0.13). Conclusion: In the 5-FU-MKN45 gastric cancer cell line model, anti-tumor pathway of Δ133p53 isomers is related with MDM2 but was not related with cyclin G1.

Key words: 5-FU, Gastric cancer, Δ133p53, MDM2, Cyclin G1