Ad-fRNK and Ad-p53 cooperate to augment drug-induced death of a transformed cell line.
BACKGROUND
Transformed cells have abnormalities in the survival pathways contributing to drug resistance. These abnormalities include p53 mutations and increased focal adhesion kinase (FAK) expression. Because FAK regulates cell survival via p53-dependent and -independent pathways, it was hypothesized that combined therapy using wild-type p53 and an inhibitor of FAK (FRNK) would sensitize cells to anticancer drugs.


METHODS
RPMI 2650 cells were infected with recombinant adenoviruses causing overexpression of p53 (Ad-p53) and FRNK (Ad-FRNK). Cell viability and apoptosis were measured using in vitro assays, whereas protein expression was determined by Western blotting.


RESULTS
Co-infection of cells with Ad-p53 and Ad-FRNK induced more cellular apoptosis than transfection with either agent alone. Likewise, the co-transfection of cells with Ad-FRNK and Ad-p53 improved the cytotoxic response to four commonly used anticancer drugs relative to cells transfected with Ad-FRNK alone, Ad-p53 alone, or the equivalent amount of control adenovirus. This effect was associated with loss of endogenous FAK protein.
Kornberg
Lori
L
Department of Otolaryngology, University of Florida, Gainesville, FL 32610, USA. kornblj@ent.ufl.edu
D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000628:therapy* / Q000821:virology; D002461:Cell Line, Transformed; D003131:Combined Modality Therapy; D005047:Etoposide / Q000494:pharmacology; D005472:Fluorouracil / Q000008:administration & dosage; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy* / Q000821:virology; D006801:Humans; D017239:Paclitaxel / Q000008:administration & dosage; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism
C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D005047:Etoposide; C113183:FAK-related nonkinase; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D017239:Paclitaxel; D005472:Fluorouracil