Determinants of cisplatin and irinotecan activities in human lung adenocarcinoma cells: evidence of cisplatin accumulation and topoisomerase I activity.

To elucidate the sensitivity of adenocarcinoma of the lung to cisplatin and irinotecan, intracellular glutathione (GSH) and glutathione S-transferase (GST)-pi concentrations and topoisomerase (topo) I activity were investigated using six adenocarcinoma cell lines. The antiproliferative activity was determined by MTT assay in terms of inhibition concentration (IC50) values. The IC50 values to cisplatin were not correlated with the amounts of intracellular GSH or GST-pi, but with intracellular accumulation of platinum (r = -0.

Establishment of a 7-ethyl-10-hydroxy-camptothecin-resistant small cell lung cancer cell line.

Irinotecan is one of the most active drugs used in the treatment of small cell lung cancer (SCLC). 7-Ethyl-10-hydroxy-camptothecin (SN-38) is an active metabolite of irinotecan. We established an SN-38-resistant subline (SBC-3/SN-38) by continuous exposure of SN-38 to a human SCLC cell line, SBC-3.

Cisplatin down-regulates topoisomerase I activity in lung cancer cell lines.

Many clinical studies have reported that irinotecan has reproducible antitumor activity against lung cancer. Both cisplatin and SN-38 are key drugs in the treatment of lung cancer, and their combination is one of the most promising regimens available. Using lung cancer cell lines, ABC-1 and SBC-3, we examined the cytotoxic effect of the schedule, as well as the effect of cisplatin on topoisomerase I activity.

Synergistic effects of topoisomerase I inhibitor, 7-ethyl-10-hydroxycamptothecin, and irradiation in a cisplatin-resistant human small cell lung cancer cell line.

7-ethyl-10-[4-(1-piperidyl)-1-piperidyl] carbonyloxy-camptothecin, a topoisomerase I (topo I) inhibitor, is one of the most active agent against lung cancer, and its radiosensitizing effect has been reported recently. We evaluated a combination in vitro effect of irradiation and 7-ethyl-10-hydroxy-CPT (SN-38), an active metabolite of 7-ethyl-10-[4- (1-piperidyl)-1-piperidyl] carbonyloxy-camptothecin, on a human small cell lung cancer cell line (SBC-3) and its cisplatin-resistant subline (SBC-3/CDDP). Growth-inhibitory effects of irradiation with or without SN-38 were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.