IMMUNOSUPPRESSIVE DRUGS AND THEIR EFFECT ON EXPERIMENTAL TUMOR-GROWTH

The effect of cyclosporin (CYA), FK 506, and mycophenolate mofetil (MP M) on tumor growth was investigated using syngeneic mouse colon carcin oma 38. Mice were laparotomized and the tumor cells were injected into the portal vein to establish liver metastasis. The animals were group ed as follows: groups A-1, B-1, and C-1 were given CyA [15 mg/kg body weight (BW)], FK 506 (0.15 mg/kg BW), and MPM (100 mg/kg BW), respecti vely, 30 min before tumor inoculation and daily for 5 days by gavage; groups A-2, B-2, and C-2 were given CyA (30 mg/kg BW), FK 506 (0.3 mg/ kg BW), and MPM (200 mg/kg BW), respectively, with the same dose timin g; and groups A-3, B-3, and C-3 received CyA (30 mg/kg BW), FK 506 (0. 3 mg/kg BW), and MPM (200 mg/kg BW), respectively, on the 7th post-tum or inoculation day and on the following 5 days. The mean tumor diamete r in groups A-1 and A-2 was greater than that in the control group and in groups C-1 and C-2 at 3 weeks (P < 0.05). The mean tumor numbers i n groups A-1 and A-2 were greater than those in the control group and in groups C-1 and C-2 at 4 weeks (P < 0.05). With in vitro MTT assay, all three drugs acted cytostatically on tumor cells with a higher conc entration (10(-6)-10(-4) mol/l), while no cytostatic effect was noted with CyA at a lower concentration (10(-9)-10(-7) mol/l). Labeling inde xes (%) by bromodeoxyuridine (BrdUrd) immunohistochemistry in groups A -1, A-2, and B-1 were significantly greater than those in the control group and in groups C-1 and C-2 (P < 0.05). Although the mechanism of cytoproliferative action of CyA and FK 506 is not well understood, a d ecrease in immunosurveillance capability by natural kill cells due to suppression of interleukin-2, their direct action as growth factors, a nd/or enhanced tumor cell adhesion can be considered.