Overexpression of protein kinase A - RIalpha reduces lipofection efficiency of cisplatin-resistant human tumor cells.
Cisplatin-resistant variant A2780CP/vector cells were 4.0-5.3-fold more transfectable and 7.6-fold more resistant to cisplatin than their parent cisplatin-sensitive human ovarian carcinoma A2780/vector cells. Overexpression of cAMP-dependent protein kinase Type I regulatory alpha subunit (PKA-RIalpha) gene in A2780CP cells significantly reduced (maximum 47.0%) the transfection activity, with a slight reduction (maximum 27.3%) of cisplatin resistance, of A2780CP cells. However, RIalpha-overexpressing A2780CP (A2780CP/RIalpha) cells were still 2.5-to 3.0-fold more transfectable and 5.5-fold more resistant to cisplatin than A2780 cells. This results suggest that gene transfer efficiency is associated with cisplatin resistance, in part, through the PKA-mediated cAMP signal transduction pathway.
Department of Pharmaceutics, Rutgers, The State University of New Jersey, College of Pharmacy, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA. KSON48@aol.com
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D000970:Antineoplastic Agents / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology*; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D017868:Cyclic AMP-Dependent Protein Kinases / Q000096:biosynthesis / Q000502:physiology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D018014:Gene Transfer Techniques; D006801:Humans; D008081:Liposomes; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology; D014162:Transfection; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D008081:Liposomes; C517834:PRKAR1A protein, human; D017868:Cyclic AMP-Dependent Protein Kinases; D002945:Cisplatin