RRC ID 42418
著者 Endo K, Kohnoe S, Tsujita E, Watanabe A, Nakashima H, Baba H, Maehara Y.
タイトル Modulation of anti-apoptosis by endogenous IAP expression in MKN45 human gastric cancer cells.
ジャーナル Anticancer Res
Abstract BACKGROUND:This study was designed to clarify differences in apoptotic signal transduction between gastric cancer cells and leukemia cells.
MATERIALS AND METHODS:In order to study apoptotic signal transduction of gastric cancer cells, MKN45 gastric cancer cells expressing the wild-type p53 gene and U937 myeloid leukemia cells expressing a mutated p53 gene were prepared. Cisplatin (CDDP) was used to induce apoptosis. We compared apoptotic signal transduction downstream to mitochondria between those two lines.
RESULTS:In contrast to U937 cells, MKN45 gastric cancer cells revealed delayed response in release of mitochondrial cytochrome c into the cytosol following caspase 3 activation. In signal pathways downstream of caspase 3 cleavage, of the three substrates detected, poly (ADP-ribose) polymerase (PARP) and PKC (protein kinase c) delta were not activated in MKN45 cells compared with U937 cells, resulting in delayed appearance of DNA ladder formation during CDDP-induced apoptosis. MKN45 constitutively expressed cLAP1, regardless of CDDP treatment, compared with no expression in U937 Drug sensitivity testing showed that MKN45 was more resistant to CDDP than U937 cells.
CONCLUSION:We demonstrated that there is a delayed mitochondrial response and incomplete activation of caspase 3 in MKN45 gastric cancer cells compared with U937 leukemia cells. In addition, there was endogenous cLAP1 expression in MKN45 cells, which may be a factor in the presumed anti-apoptotic system in these human gastric cancer cells.
巻・号 25(4)
ページ 2713-7
公開日 2005-1-1
PMID 16080516
MeSH Apoptosis / drug effects Apoptosis / physiology* Apoptosis Regulatory Proteins Caspase 3 Caspases / metabolism Cell Line, Tumor Cisplatin / pharmacology Cytochromes c / metabolism Drug Screening Assays, Antitumor Enzyme Activation Humans Inhibitor of Apoptosis Proteins Mitochondria / metabolism Poly(ADP-ribose) Polymerases / metabolism Protein Kinase C / metabolism Protein Kinase C-delta Proteins / metabolism Proteins / physiology* Stomach Neoplasms / drug therapy Stomach Neoplasms / enzymology Stomach Neoplasms / metabolism* Stomach Neoplasms / pathology* U937 Cells
IF 1.994
引用数 4
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞