title: Bcl-2 plays a key role instead of mdr1 in the resistance to hexadecylphosphocholine in human epidermoid tumor cell line KB.
abstract: We induced tolerance to hexadecylphosphocholine (HePC) in the human epidermoid tumor cell line, KB. After 70 weeks of adaptation, the IC50 of HePC in the resistant cells KBr was 32-fold higher than in parental KB cells, and they were 30-fold more resistant to another ether lipid analogue, ET-18-OCH3. The KBr cells also showed cross-resistance to vincristine and colchicine while remaining sensitive to other chemotherapy agents. RT-PCR assays showed that expression of the multidrug resistance gene (MDR1) was positive in KBr cells, whereas the expression of GST-pi (glutathione S-transferase pi) and MRP (multidrug resistance protein) was undetectable in KBr cells. Both an immunocytochemistry test and Western blot analysis indicated that the expression of bcl-2 in KBr cells was strongly positive, while it was only mildly expressed in KB cells. Verapamil could not reverse the resistance of KBr to HePC although it is a well-known reversing agent against MDR1. Our results suggest that bcl-2 instead of MDR1 plays a major role in the resistance of KBr cells.
authors.affiliation: Institute of Radiation Medicine, Beijing, People's Republic of China.
authors.forename: D
authors.initials: D
authors.lastname: Fu
authors.forename: Z
authors.initials: Z
authors.lastname: Shi
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell; D015195:Drug Design; D004351:Drug Resistance / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects; D019450:Genes, MDR; D019254:Genes, bcl-2; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D007527:Isoenzymes; D012333:RNA, Messenger; D010767:Phosphorylcholine; C039128:miltefosine; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase