Human chorionic gonadotropin (HCG) induction of apoptosis in breast cancer

Abstract

10658 Background: Apoptotic induction in cancer cells may improve the efficacy of local or systemic therapy. Human Chorionic Gonadotropin (HCG) injection directly into Kaposi’s sarcoma or melanoma has been shown to increase the apoptotic index in these tumor types. The rapid induction of apoptosis in breast cancer immediately preceding local or systemic therapy may improve the response to therapy or local control. We hypothesized that HCG would rapidly increase the apoptotic index in breast cancer after intratumoral injection. The primary objective of this preclinical trial was to determine if intratumoral injection of HCG would significantly increase the apoptotic index in breast cancer xenografts. Methods: Using a human breast cancer xenograft model in Nude mice, 5 × 106 SK-BR3 human breast cancer cells were injected subcutaneously into each flank of nu/nu mice. When the tumors reached 6 mm, 50 uL (100 U/mL) of non-recombinant, naturally occuring HCG (A.P.L., Wyeth) or saline vehicle control was injected directly into the xenograft tumors. After 24 hrs, the tumors were harvested, and the xenografts tested for proliferation (Ki-67) and apoptosis (by TUNEL assay). The apoptotic index was calculated (apoptosis/proliferation) and statistical analysis performed using paired T-test. Results: Seven pairs of SK-Br3 xenografts were tested. There were no differences in proliferation by Ki-67 determination between control or treated xenografts. Apoptosis increased in HCG treated xenografts compared to vehicle controls. Apoptosis increased from a mean of 5% (range 1– 20%) in control xenografts to a mean of 28% (range 1–70%) in HCG treated tumors (p = 0.038). Conclusions: Naturally-derived HCG induces apoptosis in human breast cancer xenografts after intratumoral injection. Substantial induction of apoptosis may improve the efficacy of local and systemic therapy in breast cancer. Injection of HCG into breast tumors immediately prior to surgical, radiation, or systemic therapy has the potential to improve local control or response to treatment. Futher elucidation of potential synergy with therapeutic modalities is justified. No significant financial relationships to disclose.