Qishen Shuangbai formula suppresses triple-negative breast cancer progression through promoting ADRA2A expression

Triple-negative breast cancer (TNBC) exhibits a particularly high degree of aggression, and traditional Chinese medicine has demonstrated encouraging outcomes in the treatment of TNBC. This study aimed to elucidate the mechanisms by which Qishen Shuangbai formula (QSF), consisting of eight herbs, inhibits TNBC progression. MDA-MB-231 and BT549 cells were subjected to treatment with QSF at different concentrations. After bioinformatics analysis, the influence of alpha-2 A adrenergic receptor (ADRA2A)-mediated PI3K/AKT signaling on TNBC cells was verified using lentiviruses and the pathway inhibitor LY294002. A xenograft tumor model was established in nude mice via subcutaneous injection of MDA-MB-231 cells that had or had not undergone lentiviral infection, followed by QSF gavage to evaluate tumor growth. QSF inhibits the proliferation, migration, and invasion of TNBC cells while enhancing their apoptosis concentration-dependently. In vivo, it suppressed TNBC tumor growth, enhanced apoptosis, and reduced Ki67 expression in tumor tissues. QSF promoted expression of ADRA2A in TNBC cells, and elevated ADRA2A expression inhibited activation of the PI3K/AKT signaling pathway. Downregulating ADRA2A weakened the antitumor activity of QSF in TNBC cells. Treatment with the PI3K/AKT signaling inhibitor LY294002 also reduced the proliferation, migration, and invasion capabilities of TNBC while increasing apoptosis in the presence of ADRA2A knockdown. This study provides evidence that the inhibition of TNBC progression by QSF is related to the ADRA2A-mediated PI3K/AKT signaling pathway, which may shed light on exploiting QSF as a novel therapeutic agent for TNBC.