Abstract
BackgroundTraditional beliefs of androgen’s stimulating effects on the growth of prostate cancer (PCa) have been challenged in recent years. Our previous in vitro study indicated that physiological normal levels of androgens inhibited the proliferation of PCa cells. In this in vivo study, the ability of testosterone (T) to inhibit PCa growth was assessed by testing the tumor incidence rate and tumor growth rate of PCa xenografts on nude mice.MethodsDifferent serum testosterone levels were manipulated in male nude/nude athymic mice by orchiectomy or inserting different dosages of T pellets subcutaneously. PCa cells were injected subcutaneously to nude mice and tumor incidence rate and tumor growth rate of PCa xenografts were tested.ResultsThe data demonstrated that low levels of serum T resulted in the highest PCa incidence rate (50%). This PCa incidence rate in mice with low T levels was significantly higher than that in mice treated with higher doses of T (24%, P < 0.01) and mice that underwent orchiectomy (8%, P < 0.001). Mice that had low serum T levels had the shortest tumor volume doubling time (112 h). This doubling time was significantly shorter than that in the high dose 5 mg T arm (158 h, P < 0.001) and in the orchiectomy arm (468 h, P < 0.001).ConclusionThese results indicated that low T levels are optimal for PCa cell growth. Castrate T levels, as seen after orchiectomy, are not sufficient to support PCa cell growth. Higher levels of serum T inhibited PCa cell growth.
Highlights
Traditional beliefs of androgen’s stimulating effects on the growth of prostate cancer (PCa) have been challenged in recent years
In this in vivo study, the ability of testosterone to inhibit PCa growth was assessed by testing the tumor incidence rate and tumor growth rate of PCa xenografts on nude mice with different serum T levels manipulated by orchiectomy or implanting different dosages of T pellets subcutaneously
In our previous in vitro study, we demonstrated that the effects of androgen on the proliferation of PCa cells possessed a biphasic pattern, which showed that androgen was essential for the growth of PCa cells, while physiological low levels of androgen were optimal for PCa cell growth, normal and higher levels of androgens inhibited PCa cell growth
Summary
Traditional beliefs of androgen’s stimulating effects on the growth of prostate cancer (PCa) have been challenged in recent years. Our previous in vitro study indicated that physiological normal levels of androgens inhibited the proliferation of PCa cells In this in vivo study, the ability of testosterone (T) to inhibit PCa growth was assessed by testing the tumor incidence rate and tumor growth rate of PCa xenografts on nude mice. Our previous study indicated that physiological normal levels of androgen inhibit the proliferation of PCa cells in vitro, though low levels of androgen are essential for initial growth of PCa cells [10] In this in vivo study, the ability of testosterone to inhibit PCa growth was assessed by testing the tumor incidence rate and tumor growth rate of PCa xenografts on nude mice with different serum T levels manipulated by orchiectomy or implanting different dosages of T pellets subcutaneously
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