Growth Inhibiting Effect of the Combination of CDDP and 5-FU on Gastric Cancer Cell Lines

• Published in: The Showa University Journal of Medical Sciences Vol. 14; no. 1; pp. 1 - 8
• Main Authors: KANO, Maiko, MARUYAMA, Hiroko, FUKUCHI, Kunihiko, GOMI, Kunihide
• Format: Journal Article
• Language: English
• Published: The Showa University Society 2002
• Subjects: 5-FU; CDDP; p21; p53; pRB
• ISSN: 0915-6380; 2185-0968
• DOI: 10.15369/sujms1989.14.1

The drug combination of cis-dichlorodiammineplatinum (II) ( CDDP ) and 5-fluorouracil (5-FU) is widely used in various cancer treatments. To better understand the benefits of this treatment regime, we analyzed the cell cycle profiles and p53-p21-pRB cascade in three gastric cancer cell lines : MKN45, MKN74 (both expressing wild type p53), and MKN28 (expressing a mutant p53) . Treatment with the drug combination caused different responses in the MKN45 and MKN74 cell lines : MKN45 cells accumulated in the G1 phase of the cell cycle and showed fewer cells in the S phase. MKN74 cells accumulated at the G1-S transition. CDDP alone caused G2-M arrest in both cell lines. The drug combination did not affect the p53 levels but increased the p21 protein levels in both cell lines. Corresponding to the G1 accumulation, unphosphorylated pRB was predominant in the MKN45 cells, and corresponding to the observed S-G2M retardation, phosphorylated pRB was predominant in the MKN74 cells. No drug combination effect was observed in MKN28 cells. These results suggest that there are several sites of action for the drug combination in cells expressing wild-type p53 and indicate that the combined drug effect is greater in cells expressing wild-type p53 than in those expressing a mutant p53.