Abstract / Summary
Abstract Triple-negative breast cancer (TNBC) is an aggressive malignancy that lacks targeted therapies and relies on cytotoxic chemotherapy. Doxorubicin (DX) is a cornerstone anthracycline for TNBC, but its clinical use is limited by dose-dependent toxicity. Boric acid (BA), a boron derivative abundant in mammalian tissues, possesses antioxidant, anti-inflammatory and anticancer properties. This study investigated whether BA potentiates the antitumoral and anti-inflammatory effects of DX in a 4T1 TNBC model. In vitro proliferation and scratch-migration assays were performed on 4T1 cells across six groups comprising BA (6 and 60 µM), DX (1.2 µM) and their combinations. For the in vivo phase, 40 female BALB/c mice bearing orthotopic 4T1 tumours were assigned to Tumour Control (TC), Doxorubicin (DX, 5 mg/kg/week i.p.), Boric Acid (BA, 2 mg/mL oral) and Combination (DB) groups. After 30 days, primary tumour, lung, liver and kidney tissues were examined histopathologically and immunohistochemically (Ki-67, eNOS, caspase-3, VEGF, TNF-α; H-score). DX inhibited proliferation dose-dependently (IC₅₀ = 12.3 ± 2.8 nM), and BA + DX markedly enhanced migration inhibition. In vivo, the DB group showed the lowest tumour volume (p < 0.0001 versus TC) and better weight stabilisation. Ki-67, VEGF and NOS H-scores were most strongly suppressed and caspase-3 activity was highest in the DB group across all tissues (p < 0.0001), whereas TNF-α expression was systematically lowest and organ architecture best preserved. Boric acid synergistically enhanced the antitumoral and anti-inflammatory effects of doxorubicin and may attenuate systemic organ toxicity, supporting its potential as an adjuvant agent in TNBC chemotherapy.