The relationship between cisplatin-induced apoptosis and p53, bcl-2 and bax expression in human lung cancer cells

Given the roles of bcl-2, bax and p53 in apoptosis, we investigated the effect of their expression on the response to cisplatin in order to understand the molecular events of cisplatin-resistance in lung cancers. Three parental human lung cancer cell lines (PC9, PC14 and H69) and their in vitro sele...

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Published in:The Korean journal of internal medicine 1999, Vol.14 (1), p.42-52
Main Authors: Han, J Y, Chung, Y J, Park, S W, Kim, J S, Rhyu, M G, Kim, H K, Lee, K S
Format: Article
Language:English
Subjects:
Antineoplastic Agents - pharmacology
Apoptosis - drug effects
Apoptosis - genetics
bcl-2-Associated X Protein
Cisplatin - pharmacology
Drug Resistance
Gene Expression
Genes, bcl-2
Genes, p53
Humans
Lung Neoplasms - drug therapy
Lung Neoplasms - genetics
Lung Neoplasms - pathology
Original
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins c-bcl-2
Tumor Cells, Cultured
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Summary:Given the roles of bcl-2, bax and p53 in apoptosis, we investigated the effect of their expression on the response to cisplatin in order to understand the molecular events of cisplatin-resistance in lung cancers. Three parental human lung cancer cell lines (PC9, PC14 and H69) and their in vitro selected cisplatin-resistant sublines were examined. Cells treated with cisplatin were processed for acridine orange and ethidium bromide staining and DNA gel electrophoresis for the morphologic detection of apoptosis. The endogenous levels of bcl-2, bax and p53 protein expression in lung cancer cells were assessed by Western blot analysis and DNA of polymerase chain reaction-amplified exon 5 to 8 of p53 gene was directly sequenced. H69, which had bcl-2 expression, p53 mutation and decreased expression of p53 and bax, was relatively resistant to cisplatin and delayed and reduced apoptosis. Although apoptosis was markedly reduced in cisplatin-resistant sublines compared to their parental cells, there were no significant differences in the expression of p53, bcl-2 and bax. Cisplatin-resistance was associated with the reduced cellular susceptibility to apoptosis. Cancer cells with the natural expression of bcl-2 and p53 mutation may be more resistant to cisplatin and less susceptible to apoptosis.
ISSN:1226-3303
2005-6648
DOI:10.3904/kjim.1999.14.1.42