Limited Cytotoxic Effect of Adenoviral-mediated p53 Gene Transfer in Variable Non-small Cell Lung Cancer (NSCLC) Cell Lines / 대한암학회지

ABSTRACT

PURPOSE: Cancer gene therapeutic strategy using p53 tumor suppresser gene have been suggested to be effective in many solid tumors including non-small cell lung cancer (NSCLC). To test generalized applicability, we tested a number of non-small cell lung cancer cell lines for their sensitivity to adenoviral-mediated wild-type p53 gene transfer. MATERIALS AND METHOD: Replication-incompetent recombinant adenovirus encoding wild- type p53 (Avp53) under the control of the human cytomegalovirus (CMV) promoter was constructed and the cytotoxic effectiveness was evaluated in various NSCLC cell lines. Because 20 moi (multiplicity of infection; number of active virus particle/cell number) of Avp53 showed highly-effective cytotoxicity in p53-deleted cell lines (NCI-H1299, and NCI-H358), same amount was used for other cell lines. RESULTS: Variable degree of cytotoxicity were observed in cell line with p53 mutation, but almost no effect were observed in those with will-type p53. Neither the infectivity of adenovirus, which was observed by x-gal stain after adenoviral mediated lac Z gene, nor the expression of p53 protein in infected cell, which was observed by western blot, was not the useful marker to expect the cytotoxic effect of Avp53. However, in responsive cell lines with Avp53, prominent expression of p21 protein, which was observed by western blot, was noticed. CONCLUSION: In conclusion, adenoviral-mediated wild-type p53 transfer may not be applicable to every patient with non-small cell lung cancer, especially when the tumor has wild-type p53 gene. Better method to predict the effectiveness before application and strategy to widen the applicable extent is needed.