title: Overexpression of protein kinase Cdelta enhances cisplatin-induced cytotoxicity correlated with p53 in gastric cancer cell line.
abstract: OBJECTIVE
  An important issue in cancer therapy is to investigate the mechanism for cellular sensitivity to anticancer agents such as cisplatin. Cisplatin is one of the DNA-damaging agents and several factors including p53 are related to the sensitivity to cisplatin in cancer. Protein kinase C (PKC) delta is known as a positive regulator for cisplatin-induced cell death. In our present study, we examined whether overexpression of PKCdelta and p53 increases the sensitivity of the human gastric cancer cell line, MKN28, which has a mutation of p53 gene, to cisplatin.
  
  
  METHODS
  Cell viability and DNA content were measured in MKN28 with adenovirus-mediated expression of PKCdelta and p53 after exposure to cisplatin. In addition, the active form of caspase-3 was detected by Western blotting.
  
  
  RESULTS
  Overexpression of exogenous PKCdelta did not induce cell death in MKN28 but inhibited cell growth at 1 microg/ml cisplatin as compared to that by cisplatin alone. Moreover, overexpression of both wild-type p53 and exogenous PKCdelta in MKN28 increased cisplatin-induced cell death in MKN28.
  
  
  CONCLUSIONS
  These results suggest that PKCdelta, in cooperation with p53, possibly regulates cisplatin-induced caspase-3-mediated cell death in gastric cancer.
authors.affiliation: Third Department of Surgery, Tokyo Medical University, Tokyo, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Iioka
authors.forename: Kenji
authors.initials: K
authors.lastname: Mishima
authors.forename: Nakanobu
authors.initials: N
authors.lastname: Azuma
authors.forename: Akihiko
authors.initials: A
authors.lastname: Tsuchida
authors.forename: Yu
authors.initials: Y
authors.lastname: Takagi
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Aoki
authors.forename: Ichiro
authors.initials: I
authors.lastname: Saito
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D051745:Protein Kinase C-delta; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D002945:Cisplatin