Expression of drug-resistant factor in renal cell cartinoma and overcoming the drug-resistance by treatment with a conjugate of doxorubicin with glutathion

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 13671675
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: JIKEI UNIVERSITY SCHOOL OF MEDICINE
• Principal Investigator: ASAKURA Tadashi JIKEI UNIVERSITY SCHOOL OF MEDICINE, LECTURER, 医学部, 講師 (30138705)
• Co-Investigator(Kenkyū-buntansha): ASANO Koji JIKEI UNIVERSITY SCHOOL OF MEDICINE, LECTURER, 医学部, 講師 (50222584)
• Project Period (FY): 2001 – 2002
• Keywords: DRUQ-BESISTANCE / GST-_II / RENAL CELL CARTINOMA / PGP / MRP / γGCS / γGCS

Research Abstract

Expression of some drug resistant factors (Pgp/MRPl/γGCS/V-ATPase/CRR9) and sensitivity of anticancer drugs against normal human renal proximal tubule epithelial cells (RPTEC) and some renal cancer cells (RCC) were studied. Overexpression of Pgp, γGCS and CRR9 in RCW, Pgp, MRP1 and CRR9 in OS2, Pgp, MRPl and CRR9 in 14TKB were observed in comparison with those in RPTEC. GST activity in each cells was corresponded to GST-_II expression (OS2>RPTEC>>RCW=14TKB=0). Cytotoxicity of CDDP and DXR against RCC was lowered than that against RPTEC and that against RCW was lowest in RCC. The resistance to CDDP an DXR was dependent on the expression of the factors but cytotoxicity of GSH-DXR exhibited potently withoulj the expression of drug resistant factors. Enhancement and suppression of GST-_II expression by transfection of GST-_II sense and antisense cDNA into the cells showed the relation of drug resistance to CDDP and DXR but little change in cytotoxicity of GSH-DXR against GST-_II transfectant was observed. From the result in cytotoxicity against transfectant of site-directedly mutated GST-n which mutated in active center (W38H or C47S), the active Center of GST-_II molecule was necessary to exhibit the drug-resistance by GST-_II.