Antiproliferative Effects of Interferons -α and -β in Combination with 5-Fluorouracil, Cisplatin, andCis- andTrans-Retinoic Acid in Three Human Lung Carcinoma Cell Lines

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Abstract
We assessed the antiproliferative effect of human recombinant interferon-α (IFN-α) or -β in combination with 5-fluorouracil (5-FU), cisplatin, or cis- or trans-retinoic acid on two human nonsmall cell lung carcinoma cell lines (SK-LU-1 and SK-MES-1) and on one human small cell lung carcinoma cell line (NCI-H69). Results were obtained by direct cell count and/or by the clonigenic assay. The three cell lines differed in their sensitivities to the antiproliferative effects of the different agents. However, both NSCLC cell lines were more responsive to IFN-β than to IFN-α. The SK-MES cell line was more resistant to both IFNs than the SK-LU-1. The NCI-H69 cells were resistant to all the drugs tested, except trans-retinoic acid. The dose and time of exposure were found to be important factors in the case of IFNs and cytotoxic agents, with lower surviving fractions obtained with the higher doses and longer exposures. This finding, however, did not hold true for the retinoic acids, which showed no antiproliferative effect. Within the sensitivity of our system, we did not identify any synergistic interaction in any of the cell lines with IFN-α or IFN-β and 5-FU or cisplatin. A slight synergistic interaction was observed with IFN and cis- or trans-retinoic acid in the SK-LU-1 cell line which was not thought to be clinically significant. We conclude that the clinically significant synergistic antiproliferative effects that have been reported with combinations of IFNs and cytotoxic agents or retinoic acids in other cancer cell lines were not observed in these three lung carcinoma cell lines.