926 - Ganoderic acids BT-01, a galectin-1 inhibitor, suppresses ovarian cancer growth in humanized mouse xenograft model.

Background

Ovarian cancer is the leading cause of death from gynaecological malignancies. Galectin-1 has been implicated in cancer progression and metastasis, and associated with poor prognosis in ovarian cancer. It is evidence that galectin-1 participates in tumor progression by evoking T cell anergy and contribute to cancer-immune escape. Ganoderma lucidum has been reported to exhibit anticancer properties. BT-01, a ganoderic acid composition, was purified from Ganoderma lucidum consisting of ganoderic acids P, Q, T, S, R, Me and ganodermic acid S. In this study, the potential role of BT-01 on inhibition of galectin-1 expression and tumor growth in ovarian was investigated.

Methods

In vitro experiments were conducted to elucidate the effectiveness of BT-01 on galectin-1 expression, and in vivo studies were to evaluate the tumor growth and immune responses. The galectin-1 expression of ovarian cancer cells ES-2 treated with BT-01 was examined by real-time PCR and western blot. Peripheral blood mononuclear cells (PBMCs) isolated from healthy donors were injected intraperitoneally into mice to establish the humanized advanced immunodeficiency mice model (Hu-PBMCs-mice). Measurement of tumor volume was determined by CT imaging, expression levels of galectin-1 and T cell infiltration in tumor tissue were examined by immunohistochemical analysis.

Results

A significant cytotoxic effect of BT-01 on ES-2 and its inhibition role on galectin-1 expression were detected in vitro. The tumor volume was decreased after treating with BT-01 in the immunodeficient mice, indicating the inhibition ability of BT-01 on tumor growth even with a defective immune system. Additionally, the tumor inhibition rate was increased in Hu-PBMCs-mice with BT-01 administration in comparison with non-humanized mice. Our findings suggested the tumor suppression effect of BT-01 which significantly decreased the expression level of galectin-1and enhanced T cell infiltration of tumor tissue in Hu-PBMCs-mice.

Conclusions

The study showed that BT-01, a potential galectin-1 inhibitors, suppressed the tumor growth and induced immune response to trigger synergistic effects for anti-cancer.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

λ Trineo Biotechnology Co., LTD.

Funding

λ Trineo Biotechnology Co., LTD.

Disclosure

All authors have declared no conflicts of interest.