Comparative effects of selected drug combinations on the growth of a human pancreatic carcinoma cell line (MIA PaCa-2).
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 X 10(-8) M vincristine (VCR) or vindesine (VDS) followed by 2 X 10(-8) M 1,2-dihydroxy-9,10-anthracenedione (DHAD) or 3 X 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 X 10(-5) M 5-fluorouracil (FUra) followed by 2 X 10(-8) M DHAD or 3 X 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 X 10(-8) M VCR and 1.6 X 10(-5) M FUra had a synergistic effect, regardless of the sequence or the time interval between the two drugs.
Fountzilas
G
G
Gratzner
H
H
Lim
L O
LO
Yunis
A A
AA
D000880:Anthraquinones / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D004317:Doxorubicin / Q000008:administration & dosage; D004357:Drug Synergism; D005434:Flow Cytometry; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008942:Mitoxantrone; D010190:Pancreatic Neoplasms / Q000473:pathology*; D014750:Vincristine / Q000008:administration & dosage; D014751:Vindesine / Q000008:administration & dosage
D000880:Anthraquinones; D014750:Vincristine; D004317:Doxorubicin; D008942:Mitoxantrone; D014751:Vindesine; D005472:Fluorouracil