Exp Mol Med.  2000 Mar;32(1):23-28.

Enhanced induction of Bax gene expression in H460 and H1299 cells with the combined treatment of cisplatin and adenovirus mediated wt-p53 gene transfer

• Choi JH
• Ahn KS
• Kim JG
• Hong YS

Abstract

Cytotoxic effect of either cisplatin or p53 gene transfection of lung cancer cells may be different depending on the p53 status of cells. We investigated cytotoxic effects on the combined treatment of cisplatin and adenovirus mediated p53 gene transfer (Avp53) in both H460 and H1299 cells in vitro. The results showed the highest numbers of apoptotic cells in both H460 and H1299 cells following the combined treatment regardless of p53 status in comparison with either cisplatin or Avp53 alone. The expression levels of p53, p21, Bax and ICE were examined to understand a possible cellular signal path of the combined treatment. In western analyses, the patterns of phosphorylated p53 protein were different between Avp53 and combined treatment. The expressions of p21 and Bax were increased in combined treatment, whereas the cleaved form of ICE (20 kD) was not detected. These results suggest that cisplatin induced p53 protein phosphorylation and may activate the downstream of p53 gene expression such as p21 and Bax. The enhanced apoptosis of lung cancer cells by the combined treatment may be useful in the development of clinical therapeutic modality of lung tumors.

Keyword

apoptosis; Avp53; Bax; cisplatin; combined treatment

MeSH Terms

Adenoviridae/genetics
Antineoplastic Agents/pharmacology*
Apoptosis/genetics
Apoptosis/drug effects
Blotting, Northern
Carcinoma, Non-Small-Cell Lung/therapy
Carcinoma, Non-Small-Cell Lung/pathology
Carcinoma, Non-Small-Cell Lung/genetics
Cell Division/genetics
Cell Division/drug effects
Cell Survival/genetics
Cell Survival/drug effects
Cisplatin/pharmacology*
Gene Expression Regulation, Neoplastic/drug effects
Gene Transfer Techniques*
Genetic Vectors
Human
Lung Neoplasms/therapy
Lung Neoplasms/pathology
Lung Neoplasms/genetics
Protein p53/genetics*
Proto-Oncogene Proteins/genetics*
RNA, Neoplasm/metabolism
RNA, Neoplasm/genetics
RNA, Neoplasm/drug effects
Tumor Cells, Cultured