[Modulation of cisplatin cytotoxicity by amphotericin B in six human cell lines of medullary thyroid cancer].
Medullary thyroid carcinoma (MTC) is frequently resistant to chemotherapy. In this work, we have studied the effect of cisdiamminedichloroplatinum (II) (CDDP) in six MTC human cell lines and we have tried to reverse the resistance to CDDP with amphotericin B (AmB). We also studied the metabolism of glutathione (GSH) and the presence of the glutathione-sulfotransferase pi (GST pi) mRNA in the MTC cell lines. The cisplatin-induced cytotoxicity was evaluated with the 3-4,5 dimethylthiazol-2,5 diphenyl tetrazolium bromide (MTT) test, the neutral red (NR) uptake and with total GSH measurement in six cell lines, TT cell line and five cell lines that we isolated. The cultures were performed with or without AmB (5 micrograms/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 different cell lines. A CDDP-induced cytotoxicity was obtained in the six cell lines at doses inhibiting 50% of the cellular proliferation (IC50) varying from 6 to 40 micrograms according to the tests and the cells tested. A low concentration of AmB (5 micrograms/mL) potentiated the cisplatin toxicity after a 48-h coincubation of TMC in all cases. GSH levels in TMC cell lines were identical to those found in normal cells. GST pi mRNA was detected in all the TMC lines, except in TT cell line. In conclusion, CDDP was toxic for all the TMC cell lines and AmB potentiated this 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.
Massart
C
C
Laboratoire d'hormonologie-enzymologie, CHU de Pontchaillou, Rennes, France.
Gibassier
J
J
Le Gall
F
F
Raoul
M L
ML
Leclech
G
G
Lucas
C
C
D000666:Amphotericin B / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000633:toxicity*; D018276:Carcinoma, Medullary / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000633:toxicity*; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005978:Glutathione / Q000032:analysis; D006801:Humans; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D000666:Amphotericin B; D004317:Doxorubicin; D005978:Glutathione; D002945:Cisplatin