Abstract
We have investigated the CDDP sensitivities of two tongue cancer cell lines with differing p53 genetic status, one with wild-type p53 (SAS) and the other with mutant-type p53 (HSC-4). SAS was about 2 times more sensitive at the D10 dose and demonstrated increased p53 and Bax protein levels at 10 h after CDDP treatment on Western blot analysis. On the other hand, overexpression of p53 in HSC-4 was observed without CDDP treatment and no elevation of Bax could be detected. Apoptosis was observed after CDDP treatment in SAS but not in HSC-4 by Hoechst 33342-staining and electrophoresis methods. These findings indicate that p53 plays an important role in apoptosis as a positive regulator of Bax expression. It is suggested that p53 status may have predictive potential with regard to response to CDDP therapy.
MeSH terms
-
Apoptosis / drug effects*
-
Carcinoma, Squamous Cell / genetics
-
Carcinoma, Squamous Cell / pathology*
-
Cisplatin / pharmacology*
-
DNA, Neoplasm / genetics
-
Drug Resistance, Neoplasm
-
Genes, p53
-
Humans
-
Neoplasm Proteins / biosynthesis
-
Neoplasm Proteins / physiology*
-
Polymerase Chain Reaction
-
Polymorphism, Single-Stranded Conformational
-
Proto-Oncogene Proteins / biosynthesis
-
Proto-Oncogene Proteins c-bcl-2*
-
Tongue Neoplasms / genetics
-
Tongue Neoplasms / pathology*
-
Tumor Cells, Cultured / drug effects
-
Tumor Cells, Cultured / pathology
-
Tumor Suppressor Protein p53 / biosynthesis
-
Tumor Suppressor Protein p53 / physiology*
-
bcl-2-Associated X Protein
Substances
-
BAX protein, human
-
DNA, Neoplasm
-
Neoplasm Proteins
-
Proto-Oncogene Proteins
-
Proto-Oncogene Proteins c-bcl-2
-
Tumor Suppressor Protein p53
-
bcl-2-Associated X Protein
-
Cisplatin