EFFECT OF AMITRIPTYLIN ON THE GROWTH-KINETICS OF 2 HUMAN CANCER XENOGRAFT LINES IN NUDE-MICE

With respect to the controversial discussion of the effect of antidepressants on the development of cancer in the literature, elicited by a recent report on growth stimulating effects of antidepressants (Brandes et al, Cancer Res 52: 3796, 1992), the effect of daily doses of amitriptylin (80 mg/m2 body surface, intraperitoneally) on the macroscopic growth of two human tumor xenograft lines in nude mice was studied (a malignant. melanoma, FO-1 and a renal cell adenocarcinoma, RCC). The application of the Gompertzian difference equation to compare the growth patterns of treated and untreated tumors shows that amitriptylin does modify the growth characteristics of both lines (p<0.05). however, in opposite directions: The growth of the melanoma FO-1 is stimulated whereas that of the RCC is inhibited. The growth pattern analysis further indicates, that this difference mainly consists of the differential effect of amitriptylin on the growth retarding processes of the tumors: amitriptylin inhibits the initial intrinsic growth rate of both tumor lines, however, only in the case of the FO-1 does it inhibit simultaneously also the growth retarding process and, thus, it ultimately stimulates its growth. On the contrary the near exponential growth of the RCC is not affected by amitriptylin. However, it cannot be excluded that at least some of the tumor growth modifying effects of the present treatment may be attributed to the potentiation of the animal weight loss by amitriptylin in the tumor-bearing animals (p<0.05).