Naslov
Characterization of carboplatin-resistant sublines derived from human larynx carcinoma cells

Autori
Osmak, Maja ; Bizjak, Lidija ; Jernej, Branimir ; Kapitanović, Sanja

Izvornik
Mutation research letters (0165-7992) 347 (1995), 3-4; 141-150

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
carboplatin; larynx carcinoma

Sažetak
In human larynx carcinoma cells, resistance to carboplatin (CBDCA) was induced by continuous five-day exposure of parental lines to the increasing CBDCA concentrations in culture medium, reaching the clinical level of 9.23 mu g/ml. Three clones were selected and characterized: CBP-3, CBP-6 and CBP-7. CBP-3 clone was 2.0-fold, CBP-6 2.1-fold, and CBP-7 2.9-fold more resistant to carboplatin. The response of these sublines to different cytostatics was compared to the response of the parental cell lines to the same drug. CBP-7 and CBP-6 clones exhibited cross-resistance to cisplatin (cis-DDP), CBP-7 clone became markedly more sensitive and CBP-3 slightly more sensitive to 5-fluorouracil (5-FU), CBP-6 became sensitive to etoposide (Et), CBP-6 became sensitive and CBP-7 resistant to vinblastine (VBL). Other clones did not change change their sensitivity to cls-DDP, 5-FU, Et or VBL. None of the three clones did alter the sensitivity to mitomycin C, doxorubicin (Dox) or vincristine (VCR). There was no change in the growth rate. Glutathione (GHS) levels were elevated in all three clones, but the increase was significant only for CBP-7 clone. Similarly, the activity of glutathione transferase (GST) was elevated in all clones, but this increase was not significant for CBP-7 clone. The analysis of the of c-myc, c-Ha-ras and c-fos genes reveal no change in the c-myc expression, induction of the c-Ha-ras oncogene in CBP-6 and CBP-7 cells, and increased expression of the c-fos in CBP-6 and CPB-7 clones. The cross-resistance profiles, GSH and GST biochemistry and oncogene expression indicate that the acquired resistance to carboplatin is a complex, multifactorial process in these cells.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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