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 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.
Seki
T
T
Second Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan.
Ohba
N
N
Makino
R
R
Funatomi
H
H
Mitamura
K
K
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D016158:Genes, p53; D006801:Humans; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D000970:Antineoplastic Agents; C494826:BAX protein, human; C494811:BCL2L1 protein, human; D016895:Culture Media, Serum-Free; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D002945:Cisplatin