Abstract
The inhibitory effect of several drug combinations on the growth of the human pancreatic carcinoma cell line MIA PaCa-2 was studied in relation to drug-scheduling interval in vitro. All drug exposures were for 1 hour. The sequential exposure of cells to 1.5×10−8 M vincristine (VCR) or vindesine (VDS) followed by 2×10−8 M 1,2-dihydroxy-9,10-anthracenedione (DHAD) or 3×10−7 M adriamycin (ADR) had at best an additive effect, demonstrated by isobologram analysis, when the two drugs were given 6 hours apart. Flow cytometry (FCM) analysis after exposure of the cells to the priming drug alone, i.e., VCR or VDS, showed an accumulation of cells in S-phase. The exposure of MIA PaCa-2 cells to 1.6×10−5 M 5-fluorouracil (FUra) followed by 2×10−8 M DHAD or 3×10−7 M ADR had an additive (with DHAD) or synergistic (with ADR) effect when the two drugs were given simultaneously and a synergistic effect with either drug when they were given 2, 6, or 24 hours apart. FCM analysis after exposure to FUra alone showed a rapid S-phase accumulation appearing within 6 hours and increasing further after 24 hours. Sequential exposure of cells to 1.5×10−8 M VCR and 1.6×10−5 M FUra had a synergistic effect, regardless of the sequence or the time interval between the two drugs.
