Bipolar androgen therapy (BAT) can improve the prognosis of enzalutamide-resistant castration-resistant prostate cancer (CRPC) patients and its mechanism has not been elucidated. In order to explore the mechanism of BAT treatment and the possibility of combined immunotherapy in the future.

Using testosterone enanthate as the treatment drug, the male C57 mice castrated after bearing tumor cell line were treated with enzalutamide, and enzalutamide-resistant CRPC animal models were established. Two negative control groups (control, Castration + enzalutamide), two blank groups (blank injection, blank implant) and two experimental groups (androgen injection, androgen implant) was set up. The survival of model was observed, and enzyme linked immunosorbent assay (ELISA) was used to determine serum testosterone content. Testosterone injection and testosterone implant were used as BAT to treat enzalutamide-resistant models. The size and quality of tumors off the body were measured. The γH2AX protein was detected by Western blotting. Flow cytometry and immunohistochemistry were used to detect CD3 ⁺ T cells of the tumor tissue. GraphPad software was used for statistical analysis.

Both the injection and the implant were effective methods of releasing testosterone, which could significantly increase blood androgen levels [(31.97±2.90), (20.70±0.92) ng/ml vs. (1.14±0.43), (1.21±0.34) ng/ml, F=149.653, 40.399, P<0.05] and reduce the size of tumor [(907.60±55.95), (894.71±100.65) mm³ vs. (1 685.82±12.37), (1 642.83±8.30) mm³, F=3.744, 2.938, P<0.01]. As compared with implant method, injection method had increased concentration and testosterone level in a short time. It could cause more DNA damage (F=14.855, P<0.01), and partially increased the infiltration of CD3⁺ T cells (F=9.782, P<0.01), but the level of security was poor.

Both the implantation method and the injection method are effective in BAT. The injection method has a slightly better effect than the implant method. The injection method has a greater degree of DNA damage and causes more immune cell infiltration, suggesting combined immunotherapy with BAT may have better effect in the future.

Prostate cancer; Androgen; Model, animal