Hyperthermic modulation of resistance to cis-diamminedichloroplatinum (II) in human larynx carcinoma cells.
The aim of the present study was to examine the effect of hyperthermia on cisplatin resistance in two sublines of human larynx carcinoma HEp2 cells. Hyperthermia was tumouricidal for both parental and cisplatin resistant cells, but cisplatin resistant cells were more sensitive to the heat at 43 and 44 degrees C. In combined cisplatin-hyperthermia treatment, heat chemosensitization was observed for parental, as well as for cisplatin resistant cells. At 42 degrees C, and at 43 degrees C, the thermal enhancement ratio (TER) for cisplatin toxicity was higher in resistant than in parental cells. The heating at 42 degrees C decreased the resistance factors in CA3 and CK2 cells from 2.2 and 3.5 to 1.8 and 2.2 respectively. At 43 degrees C, the resistance factors were decreased to 1.7 for CA3 cells and 2.0 for CK2 cells. The heating at 43 degrees C increased intracellular platinum accumulation in all cell lines examined. This effect was more pronounced in resistant, than in parental cells, causing complete reversal of the reduced platinum accumulation found at 37 degrees C in resistant cells. In conclusion, the resistance to cisplatin was partially reversed by hyperthermia in CA3 and CK2 cells. Increased drug accumulation was one of the mechanisms involved in hyperthermic potentiation of cisplatin toxicity and partial reversal of cisplatin resistance in human larynx carcinoma HEp2 cells.
Beketić-Oresković
L
L
Ruder Bosković Institute, Department of Molecular Medicine, Zagreb, Croatia.
Jaksić
M
M
Oresković
S
S
Osmak
M
M
D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000493:pharmacokinetics / Q000494:pharmacology*; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm; D006358:Hot Temperature; D006801:Humans; D006979:Hyperthermia, Induced; D007822:Laryngeal Neoplasms / Q000188:drug therapy / Q000628:therapy*; D014407:Tumor Cells, Cultured
D002945:Cisplatin