The correlation of membranous glycoprotein-gp-170, cytoplasmic glutathione and glucose-6-phosphate dehydrogenase levels with multidrug resistance in transitional cell carcinoma cell lines of the urinary tract.
The expression of membranous glycoprotein gp-170, cytoplasmic glutathione (GSH) and energy-related glucose-6-phosphate dehydrogenase (G-6-PD) in cultured normal urothelial cells and transitional cell carcinoma (TCC) cell lines was analyzed by flow cytometric and enzymatic methods. The chemosensitivity of these tumor cells to four major types of anticancer drugs, including cisplatin, thiotepa, methotrexate, 5-fluorouracil, adriamycin and vinblastine, was correlated with biological activities in TCC cell lines. The TCC cell lines displayed a general sensitivity to anticancer drugs with a low incidence of highly resistant cell lines (23%). The expression of multidrug resistance was not related to cellular differentiation or invasiveness of cancer cells. Only 24% of TCC cell lines had an elevated expression of gp-170, but their expression was not related to drug resistance. Increased cytoplasmic GSH and G-6-PD was observed in over 90 per cent of TCC cell lines, but no correlation with drug resistance and cellular differentiation was observed. The biological activities of GSH and G-6-PD were not related to the drug resistance of TCC. The low expression rate of gp-170 in TCC cells indicates that other mechanisms should be involved in the development of MDR in TCC cells.
Yu
D S
DS
Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Chang
S Y
SY
Ma
C P
CP
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000378:metabolism*; D018432:Drug Resistance, Multiple; D015972:Gene Expression Regulation, Neoplastic; D005954:Glucosephosphate Dehydrogenase / Q000096:biosynthesis*; D005978:Glutathione / Q000096:biosynthesis*; D006801:Humans; D014407:Tumor Cells, Cultured; D014571:Urologic Neoplasms / Q000188:drug therapy / Q000378:metabolism*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D005954:Glucosephosphate Dehydrogenase; D005978:Glutathione