Mechanism of growth-inhibitory effect of cisplatin on human pancreatic cancer cells and status of p53 gene

Pancreatic cancer is a devastating malignant tumor in humans and the develo pment of new modalities of treatment is needed. We studied the mechanism of the growth-inhibitory effect of cisplatin (CDDP) on human pancreatic cance r cells in connection with the status of the p53 gene and expression of the bcl-2 family. COLO-357 cells with wild-type p53 gene and T3M4, Panc-1 and AsPC-1 cells with mutant p53 gene were used. Growth of these cells was inhi bited by CDDP in a dose-dependent manner in both serum-deprived and serum-s upplemented conditions. CDDP induced apoptosis of COLO-357 and T3M4 cells i n the serum-supplemented condition, whereas necrosis of these cells was ind uced by CDDP at high concentrations in the serum-deprived condition. Althou gh expression of bax mRNA and its protein product were enhanced, while bcl- 2 protein was decreased by CDDP in COLO-357 cells, expression of mRNA of th e bcl-2 family and protein product were not influenced by CDDP in T3M4 cell s. Increased expression of bax and reduced expression of bcl-2 are involved in the growth-inhibitory effect of CDDP on pancreatic cancer cells with wi ldtype p53 gene.