We developed and characterized a new series of low- and high-grade multi-drug-resistant (MDR) cell lines of human esophageal carcinoma. Eight vinde-sine-resistant clones, SH-1-V1, SH-1-V2, SH-1-V3, SH-1-V4, SH-1-V5, SH-1-V6, SH-1-V7, and SH-1-V8 were isolated from the human esophageal cancer cell line, SH-1, by stepwise selection on exposure to increasing doses of vindesine. SH-1-VI to SH-1-V8 acquired resistance to vindesine, in a stepwise manner, from 3- to 115-fold over findings in the parental SH-1 cells. The most resistant clone, SH-1-V8, was cross-resistant to other anticancer agents such as vincristine, actinomycin D, and daunomycin, thereby suggesting acquisition of the MDR phenotype. In SH-1-V8 cells, cellular accumulation of vincristine decreased and an MDR reversal agent, cepharanthine, potentiated the cytoci-dal action of vindesine. The expression of MDR 1 mRNA was enhanced and amplification of the MDR1 gene was observed in clones SH-1-V4, SH-1-V5, SH-1-V6, SH-1-V7 and SH-1-V8; expression of MDR1 mRNA was detectable without gene amplification in the remaining 3 clones. The enhanced expression of the MDR1 gene may be involved in the acquisition of vindesine resistance in human esophageal cancer cells.

Keywords:
MDR1 gene, P-glycoprotein, Vindesine, Esophageal carcinoma, SH-1
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© 1994 S. Karger AG, Basel
1994
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