Reference - Detail
|Author||Uzawa K, Kasamatsu A, Baba T, Usukura K, Saito Y, Sakuma K, Iyoda M, Sakamoto Y, Ogawara K, Shiiba M, Tanzawa H.|
|Title||Targeting phosphodiesterase 3B enhances cisplatin sensitivity in human cancer cells.|
We previously reported that human squamous cell carcinoma (SCC) cell lines refractory to cis-diaminedichloro-platinum II (cisplatin [CDDP]) had significant upregulation of the phosphodiesterase 3B gene (PDE3B), suggesting that inhibiting PDE3B suppresses CDDP resistance. shRNA-mediated PDE3B depletion in CDDP-resistant cells derived from SCC cells and Hela cells and induced CDDP sensitivity and inhibited tumor growth with elevated cyclic GMP induction resulting in upregulation of the multidrug-resistant molecule, but this did not occur in the 5-fluorouracil-resistant hepatocellular carcinoma cell lines. Furthermore, the antitumor growth effect of the combination of a PDE3B inhibitor (cilostazol) and CDDP in vivo was also greater than with either cilostazol or CDDP alone, with a significant increase in the number of apoptotic and cell growth-suppressive cancer cells in CDDP-resistance cell lines. Our results provided novel information on which to base further mechanistic studies of CDDP sensitization by inhibiting PDE3B in human cancer cells and for developing strategies to improve outcomes with concurrent chemotherapy.
|MeSH||Animals Antineoplastic Combined Chemotherapy Protocols / therapeutic use Apoptosis / drug effects Body Weight / drug effects Carcinoma, Squamous Cell / drug therapy* Carcinoma, Squamous Cell / metabolism Carcinoma, Squamous Cell / pathology Cilostazol Cisplatin / administration & dosage Cisplatin / pharmacology* Cyclic AMP / metabolism Cyclic GMP / metabolism Cyclic Nucleotide Phosphodiesterases, Type 3 / biosynthesis* Cyclic Nucleotide Phosphodiesterases, Type 3 / genetics Cyclic Nucleotide Phosphodiesterases, Type 3 / physiology Dose-Response Relationship, Drug Drug Resistance, Neoplasm / drug effects Female Gene Expression Regulation, Enzymologic Gene Silencing HeLa Cells Humans Mice Mice, Nude Phosphodiesterase 3 Inhibitors / administration & dosage Phosphodiesterase 3 Inhibitors / pharmacology* RNA, Messenger / genetics Tetrazoles / administration & dosage Tetrazoles / pharmacology Tumor Cells, Cultured Uterine Cervical Neoplasms / drug therapy* Uterine Cervical Neoplasms / metabolism Uterine Cervical Neoplasms / pathology Xenograft Model Antitumor Assays / methods|
|Human and Animal Cells|