High expression of
histone deacetylase 2 (HDAC2) is recognized as a marker of invasive
breast cancer (BC). HDAC2 is not only responsible for enhancing
tumor cell growth, development, and anti-apoptosis, but also plays a significant role in regulating PD-L1 on the surface of
tumor cells. Continuous expression of PD-L1 allows
tumor cells to escape immune surveillance. There is not much research on how HDAC2 affects the immune system in
breast cancer.
Ginsenoside Rh4 (Rh4) is a major rare
saponin in heat-treated ginseng, which is widely applied in treating and preventing various diseases because of its potent medicinal value and stable safety. However, it is unclear how Rh4 affects the
tumor immune microenvironment in
breast cancer. Therefore, this paper aims to investigate the effect of Rh4 on HDAC2 in
breast cancer, specifically the effect of HDAC2 on apoptosis and the immune microenvironment to inhibit
breast cancer growth. According to our study,
ginsenoside Rh4 has been shown to significantly suppress
breast cancer cell proliferation without any adverse effects. The molecular docking results of Rh4 and HDAC2 indicate a binding energy of -6.06 kcal/mol, suggesting the potential of Rh4 as a targeting modulator of HDAC2. Mechanistically, Rh4 induces apoptosis of
breast cancer cells by the HDAC2-mediated
caspase pathway and inhibits the HDAC2-mediated JAK/STAT pathway to regulate the immune microenvironment, which inhibits
breast cancer growth. Specifically, Rh4 was shown for the first time to blockade immune checkpoints (PD-1/PD-L1) and increase levels of T-lymphocytes in the
tumor. In a word, our study establishes a theoretical framework for applying Rh4 as an
immune checkpoint inhibitor as part of
breast cancer treatment.