MODULATION OF CISPLATIN-INDUCED CYTOTOXIC ITY BY AMPHOTERICIN-B IN 6 HUMAN CELL-LINES OF MEDULLARY-THYROID CANCER

Medullary thyroid carcinoma (MTC) is frequently resistant to chemother apy. In this work, we have studied the effect of cis-diamminedichlorop latinum (II) (CDDP) in six MTC human cell lines and we have tried to r everse the resistance to CDDP with amphotericin B (AmB). We also studi ed the metabolism of glutathione (GSH) and the presence of the glutath ione-sulfotransferase pi (GST pi) mRNA in the MTC cell lines. The cisp latin-induced cytotoxicity was evaluated with the 3-4,5 dimethylthiazo l-2,5 diphenyl terrazolium bromide (MTT) rest, the neutral red (NR) up take and with total GSH measurement in six cell lines, TT cell line an d five cell lines that we isolated The cultures were performed with or without AmB (5 mu g/mL). Intracellular GSH was measured in TMC cells and compared to the levels obtained in six normal thyroid tissues. The expression of GST pi mRNA was evaluated by Northern blotting in the d ifferent cell lines. A CDDP-induced cytoxicity was obtained in the six cell lines at doses inhibiting 50% of the cellular proliferation (IC5 0) varying from 6 to 40 mu g according to the tests and the cells test ed A low concentration of AmB (5 mu g/mL) potentiated the cisplatin to xicity after a 48-h coincubation of TMC in all cases. GSH levels in TM C cell lines were identical to those found in normal cells. GST pi mRN A was detected in all the TMC lines, except in IT cell line. In conclu sion, CDDP was toxic for all the TMC cell lines and AmB potentiated th is antitumoral effect. On the contrary, GSH and GST pi do not seem to be involved in the mechanisms of the resistance in these cell lines.