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

Anticancer Res. 2001 May-Jun;21(3B):1919-24.

Abstract

Pancreatic cancer is a devastating malignant tumor in humans and the development of new modalities of treatment is needed. We studied the mechanism of the growth-inhibitory effect of cisplatin (CDDP) on human pancreatic cancer 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 inhibited by CDDP in a dose-dependent manner in both serum-deprived and serum-supplemented conditions. CDDP induced apoptosis of COLO-357 and T3M4 cells in the serum-supplemented condition, whereas necrosis of these cells was induced by CDDP at high concentrations in the serum-deprived condition. Although 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 the bcl-2 family and protein product were not influenced by CDDP in T3M4 cells. Increased expression of bax and reduced expression of bcl-2 are involved in the growth-inhibitory effect of CDDP on pancreatic cancer cells with wild-type p53 gene.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • Blotting, Western
  • Cell Division / drug effects
  • Cisplatin / pharmacology*
  • Culture Media, Serum-Free / pharmacology
  • DNA Fragmentation
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Genes, p53*
  • Humans
  • Mutation
  • Pancreatic Neoplasms / drug therapy*
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Messenger / metabolism
  • Tumor Cells, Cultured
  • bcl-2-Associated X Protein
  • bcl-X Protein

Substances

  • Antineoplastic Agents
  • BAX protein, human
  • BCL2L1 protein, human
  • Culture Media, Serum-Free
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • Cisplatin