Abstract 3624: Tanshinone IIA could decrease programmed death ligand 1 expression in human breast cancer BT-20 cells

Abstract

Abstract Breast cancer is the leading cause of cancer-related death in women. Many prescriptions for chemotherapy have been derived from plants. Danshen (Salviae miltiorrhizae radix) has been used in traditional Chinese medicine and appeared in the Chinese book, Shennong Bencao Jing (ca. 100 A.D.). Tanshinone IIA (Tan-IIA) is extracted from danshen and first described by researchers in 1968. Tan-IIA is well known to have antioxidant and anti-inflammatory properties. Tan-IIA could inhibit many human breast cancer cell lines through different molecular mechanisms in vitro and in vivo have been well documented. Our previous study showed Tan-IIA could inhibit human breast cancer cells through increased Bax to Bcl-xL ratios. Tan-IIA inhibits BT-20 (estrogen-, progesterone-, and HER2-negative subtype (TNBC)) human breast cancer cell proliferation through increasing caspase 12, GADD153 and phospho-p38 protein expression. Tan-IIA also inhibits human breast cancer MDA-MB-231 cells (estrogen-, progesterone-, and HER2-negative subtype (TNBC)) by decreasing LC3-II, Erb-B2 and NF-κBp65 in vivo. However, the effects and molecular mechanisms of Tan-IIA in human breast cancer have not been elucidated clearly. Programmed cell death-ligand 1 (PD-L1) is expressed on many cancer cells, which played a protective role against the cytotoxicity. PD-L1 interacts with programmed cell death-1 receptor (PD-1) to inhibit the T cells and block the antitumor immune response. PD-L1 antibodies, has demonstrated the possibility of dismiss immune suppression in many cancer cells. PD-L1 expression is a favorable biomarker for the prognosis of breast cancer; therefore, immune checkpoint blockade agents may be offering the opportunity to be the future treatment for breast cancer. The present study focused to evaluate the efficacy of Tan-IIA to be one of the immune checkpoint blockade agents for human breast cancer cells. Material and Method: In the present study, the human breast cancer BT-20 cells were treated with SJKJT in vitro. The effects of Tan-IIA on the protein expressions of PD-1, PD-L1, Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), B7-1 (CD80) and B7-2 (CD86) were measured by Western blotting. Results: The results showed that Tan-IIA can inhibit the protein expressions of PD-L1, in breast cancer BT-20 cells significantly. Conclusion: Breast cancer BT-20 cells were treated with Tan-IIA could inhibit the activity of PD-L1, CTLA-4, B7-1 (CD80) and B7-2 (CD86) significantly. These results suggest that one of the molecular mechanisms for Tan-IIA to inhibit breast cancer BT-20 cells maybe through inhibiting the protein expression of PD-L1. The use of Tan-IIA may become a feasible novel therapy option. Further studies are warranted to fully elucidate its mechanisms of action. Citation Format: Chin Cheng Su. Tanshinone IIA could decrease programmed death ligand 1 expression in human breast cancer BT-20 cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3624.