Association of p73 G4C14-to-A4T14 polymorphism at exon 2 with the response of human lung adenocarcinoma cell lines to chemotherapy.

摘要

In order to assess the effect of p73 gene polymorphism G4C14-A4T14 on cisplatin-based chemosensitivity of human lung adenocarcinoma cell lines, we examined the differences in biological character and drug sensitivity affected by cisplatin between human lung adenocarcinoma cell lines A549 and P15. The allelic expression of p73 in A549 and P15 was studied by Sty I polymorphism analysis. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay was used to analyse the response of these two cell lines to cisplatin. The changes in the biological behaviour of the cells were observed by colony formation assay. The drug-induced apoptosis of cells was measured by Hoechst and TUNEL techniques. Homozygous allelic expression was demonstrated in the two cell lines. AT/AT genotype appeared in A549, GC/GC genotype was detected in P15. Although the colony formation number decreased with an increasing cisplatin dose (P<0.05), there was no significant difference in colony-formation rate in these two cell lines (P>0.05). MTT assay also determined that the 50% inhibitory concentration (IC50) for A549 and P15 was 8.9 and 11.6 micromol/l, respectively; the IC50 value did not differ significantly between A549 and P15 (P>0.05). The cell apoptosis induced by cisplatin was demonstrated in both A549 and P15. P73 G4C14-A4T14 polymorphisms at exon 2 existed in human NSCLC (non-small-cell lung cancer) cell lines. Our data in vitro suggest that p73 G4C14-A4T14 polymorphism has no significant relationship to the cisplatin-based chemosensitivity in human lung adenocarcinoma.