Bcl-2 plays a key role instead of mdr1 in the resistance to hexadecylphosphocholine in human epidermoid tumor cell line KB

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.