[Experimental study of chemotherapy of renal cell carcinoma. 2. Combination effect of interferon and antitumor agents based on cell kinetic analysis].

To establish a useful combination therapy of interferon (IFN) with antitumor agents, I investigated the antiproliferative effect and change of DNA histograms in vitro after the IFN exposure either alone or in combination with antitumor agents, simultaneously or sequentially, on NC-65 cells derived human renal cell carcinoma. The IFN used was recombinant interferon alpha-2a (IFN-alpha) and the antitumor agents selected were vincristine (VCR) and adriamycin (ADM). IFN-alpha suppressed the proliferation clearly in a dose dependent manner but not so apparently even after the 96-hour exposure. Six to 12 hours after the exposure of IFN-alpha, accumulation of the cells in the G1 phase was observed at the higher concentration, and then increase of S phase cells up to 72 hours, suggesting a G1-S block at a short period and then prolongation of S-phase. VCR combined with IFN-alpha suppressed NC-65 cell proliferation additively, whereas ADM combined with IFN-alpha suppressed it rather less than additively. The sequential exposure of IFN followed by VCR induced the enhancement at a higher concentration but that followed by ADM did not, suggesting that IFN-induced cell modification made the cells more sensitive to VCR. Dose dependent accumulation in the G1-S boundary phase was observed after the combined exposure of IFN-alpha and antitumor agents, especially by sequential exposure, and then accumulation in S and G2-M were observed. The delay of cell progression in the S phase was likely significant when IFN-alpha was used with antitumor agents, such as VCR and ADM.