title: Combined effects of protein kinase inhibitors and 5-fluorouracil on CEA expression in human colon cancer cells.
abstract: Previous studies showed that 5-fluorouracil (5-FU) and Staurosporine (ST), a protein kinase inhibitor (PKI), were able to increase the expression of carcinoembryonic antigen (CEA) in human colon cancer cells. In the present study, we examined the in vitro effects of five PKIs, i.e. ST, 1-5-isoquinolinyl-sulfonyl-2-methylpiperazine (H-7), bisindolylmaleimide-I (BIS), Genistein (GEN), and Herbimycin A (HERB) alone or in combination with 5-FU on CEA expression. C22-20, a clonal subline, derived from colon cancer HT-29 line, selected for low expression of CEA, was used in our experimental model. Among the PKIs tested, only ST, at non-toxic concentrations of 5 nM, was capable of increasing the level of CEA. The other PKIs did not modify CEA expression when used either alone or in combination with 5-FU. Flow cytometric analysis showed that treatment of cells with 5-FU + ST resulted in a synergistic increase of CEA expression, being higher than that obtainable with both agents alone. Moreover, the increase of CEA expression occurred not only in membrane fractions but also in cytosolic compartments, as indicated by Western blot analysis. The present study suggests that ST-mediated induction of CEA expression in cancer cells is PKC independent and could be of potential clinical interest for the development of new diagnostic and/or immunotherapeutic approaches.
authors.affiliation: Pharmacology and Medical Oncology Section, Department of Neuroscience, University of Rome, Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.
authors.forename: Salvatore Pasquale
authors.initials: SP
authors.lastname: Prete
authors.forename: Lorena
authors.initials: L
authors.lastname: Rossi
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Correale
authors.forename: Mario
authors.initials: M
authors.lastname: Turriziani
authors.forename: Susanne
authors.initials: S
authors.lastname: Baier
authors.forename: Giuliana
authors.initials: G
authors.lastname: Tamburrelli
authors.forename: Liana
authors.initials: L
authors.lastname: De Vecchis
authors.forename: Enzo
authors.initials: E
authors.lastname: Bonmassar
authors.forename: Angelo
authors.initials: A
authors.lastname: Aquino
mesh_terms: D002272:Carcinoembryonic Antigen / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D019311:Staurosporine / Q000494:pharmacology*
chemical_list: D002272:Carcinoembryonic Antigen; D007166:Immunosuppressive Agents; D047428:Protein Kinase Inhibitors; D019311:Staurosporine; D005472:Fluorouracil