Division of Pulmonary, Critical Care, and Environmental Medicine, School of Medicine, University of Missouri, Five Hospital Drive, Columbia, MO 65212, USA. gunturv@health.missouri.edu
Anticancer Res. 2010 Sep; 30(9):3557-64.
To determine whether increasing p53 protein levels confers enhanced chemosensitivity in non-small cell lung cancer (NSCLC).
Three NSCLC cell lines, with different endogenous p53 expression, were transfected with wild-type p53 (wt-p53) or CD-1 (truncated wt-p53) genes. Cells were subsequently treated with cisplatin (CDDP) or paclitaxel (PAX). Cell viability was measured using Alamar Blue Assay.
Cells transfected with CD-1 expressed 13-38% higher levels of p53 protein compared to cells transfected with the wt-p53 gene, despite their baseline endogenous levels. CD-1-transfected cells also had higher cell death when treated with CDDP (p<0.05) or PAX, exhibiting 30-60% higher death rates than cells transfected with the wt-p53 gene and 130-160% higher than untransfected cells. A significant positive correlation between p53 protein concentration and cytotoxic response was demonstrated (R(2) for CDDP=0.823; R(2) for PAX=0.909; p<0.001).
Increasing intracellular p53 protein concentrations can augment the effect of CDDP and PAX in NSCLC, despite the baseline level of p53 protein expression.
PMID: 20944137 [PubMed - in process] Source: National Library of Medicine.
