Increasing P53 protein sensitizes non-small cell lung cancer to paclitaxel and cisplatin in vitro

Vamsi P. Guntur, J. Clifford Waldrep, Jennifer J. Guo, Kim Selting, Rajiv Dhand

Research output: Contribution to journalArticlepeer-review

Abstract

Aim: To determine whether increasing p53 protein levels confers enhanced chemosensitivity in non-small cell lung cancer (NSCLC). Materials and Methods: 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. Results: 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 (R2 for CDDP=0.823; R2 for PAX=0.909; p<0.001). Conclusion: Increasing intracellular p53 protein concentrations can augment the effect of CDDP and PAX in NSCLC, despite the baseline level of p53 protein expression.

Original languageEnglish (US)
Pages (from-to)3557-3564
Number of pages8
JournalAnticancer Research
Volume30
Issue number9
StatePublished - Sep 1 2010
Externally publishedYes

Keywords

  • Chemosensitivity
  • Chemotherapy
  • Cisplatin
  • Lung cancer
  • Paclitaxel
  • p53

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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