Paclitaxel is a key drug in cancer therapy, yet its clinical benefit is often constrained by pronounced toxicity and the development of resistance. 10-Gingerol (10-G), a naturally occurring ginger-derived molecule with known anti-inflammatory and antiproliferative actions, has been proposed as a potential chemosensitizer. However, its influence on the response of triple-negative breast cancer (TNBC) to paclitaxel has not been clearly defined. This work investigates whether 10-G can improve paclitaxel efficacy in TNBC and explores the mechanism responsible. A series of cell-based and animal experiments were conducted. CCK-8 assays and colony formation tests evaluated cell growth, while apoptosis was examined using flow cytometry and TUNEL staining. Protein-level changes were assessed by Western blotting and immunohistochemical analysis. Molecular docking, together with ADRB2 gene knockdown, was used to validate the interaction between 10-G and adrenoceptor Beta 2 (ADRB2). Toxicity was monitored in mice through body-weight measurements, organ coefficient analysis (kidney and spleen), and histopathology.10-G markedly boosted the responsiveness of TNBC cells to paclitaxel and amplified paclitaxel-triggered apoptosis. Computational docking and lentiviral silencing identified ADRB2 as a direct molecular target of 10-G, with 10-G binding to and suppressing its active domain. Loss of ADRB2 reduced TNBC cell proliferation and weakened the sensitizing influence of 10-G on paclitaxel treatment. Protein analyses indicated that 10-G mediated both growth inhibition and enhanced chemotherapy response by suppressing the ADRB2/ERK cascade. Toxicity studies showed that combining 10-G with paclitaxel did not aggravate liver or kidney injury. The findings support the potential use of 10-G as an adjuvant agent to strengthen paclitaxel-based treatment in TNBC and highlight ADRB2 as a promising target for improving chemotherapy sensitivity.
