CELL-PROLIFERATION AND APOPTOSIS DURING PROSTATIC TUMOR XENOGRAFT INVOLUTION AND REGROWTH AFTER CASTRATION

The biological mechanisms involved in androgen-dependent and -independ ent prostate cancer growth after castration were analyzed in the LuCaP 23.1 human prostate cancer xenograft model. Athymic mice (n = 82) bea ring LuCaP 23.1 xenograft were castrated and tumors were harvested at different time points from day 0 to day 112 post castration. In each g roup of mice, tumor growth rate (TGR), serum PSA concentration, percen tage of tumor cells incorporating bromodeoxyuridine (BUdR index), perc entage of apoptotic tumor cells assessed by morphological analysis (ap optotic index), and presence of apoptosis-related DNA ''ladder'' were analyzed. Castration induced a significant decrease in TGR and serum P SA from day 1 to day 7, and a progressive increase in the 2 parameters from day 14 to day 112, heralding androgen-independent tumor relapse. Meanwhile the BUdR and apoptotic indexes varied as follows after cast ration: an increase was noted for both at day 3, a significant increas e in apoptotic index with a decrease in BUdR index from day 5 to day 1 4, and a progressive decrease in apoptotic index while BUdR index rema ined at 50% of the pre-castration value from day 28 to day 112. DNA la dder was present sparsely in tumors grown in non-castrated hosts, univ ersally present in tumors from day 1 to day 28 post castration, and fr equent in tumors from day 56 to 112. Castration-induced effects in LuC aP 23.1 tumors were characterized by an increase in number of apoptoti c cells and a decrease in proliferative activity. The androgen-indepen dent tumor relapse after castration was associated with a low apoptoti c index with no increase in proliferative activity.