Methylxanthines(MeX) have been previousely reported to enhance the lethal potential of many DNA damaging agents in rodent and human tumor cells. Recently Pentoxifylline(PENT) and Caffeine, both are MeX, showed the enhancing action of cytotoxicity
of
alkylating anticancer drugs in animal models. The phenomenon attributed to the prevention of DNA repair.
Authors planned this experiment to assess the amplification o fthe anticancer effect of PENT and Caffeine in combination with one of the alkylating agents, Cyclophosphamide (CTX), for human gastric adenocarcinoma cell line(NUGC-4). The cultured
NUGC-4
gastric cancer cells embedded in fibrin clot and were implanted under the renal capsule of the immunocompetent ICR female mice(Fibrin clot subrenal capsule assay). After implantation, CTX was given 50mg/kg, s.c., on day 1 to 5, PENT, 257mg/kg,
s.c., on
2 and 3 day, and in caffeine experiment, caffeine was given 0.175mg/kg, i.p, on day 2 to 3. For immunosuppression, cyclosporin-A was given 80mg/kg, s.c., on day 2, 3 and 4 for all experimental mice. Implanted tumor size was measured on day 6
after
implantation with stereomicroscope(1mm=10omu).
@ES The results were summerized as follows:
1) Combination treatment with PENT and CTX for human gastric adenocarcinoma cells (NUGC-4) enhanced the cytotoxicity of CTX with no side effects. PENT alone revealed no anticancer effect(p=0.006).
2) Caffeine with CTX showed also enhancement of anticancer effect of CTX, Caffeine alone disclosed minimal antitumor action, however side effect was prominent with given doses.
3) Fibrin clot subrenal capsule assay thought to be a simple, fast and effective method to evaluate the efficacy of anti-tumor agent.
These results provide the evidence for a novel approach to improve the therapeutic index of CTX and other alkylating agents used for human stomach cancer.
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