Unlocking synergistic potential: enhancing paclitaxel efficacy in combination with silibinin in breast cancer cell line through H19 LncRNA and P53/Bax/Bcl2 axis

Breast cancer is a major global health concern and the second most frequently diagnosed malignancy in women. Paclitaxel, a key chemotherapeutic agent, shows strong antineoplastic activity but is limited by toxicity and resistance. While combining paclitaxel with natural compounds is promising, the role of H19 lncRNA in mediating paclitaxel-silibinin synergy is not yet known. This study evaluates their combined efficacy via modulation of H19 lncRNA and the P53/Bax/Bcl2 apoptotic pathway. We investigated the chemosensitizing effect of silibinin, a flavonoid, in combination with paclitaxel in breast cancer cells. Drug interactions were analyzed using the Chou-Talalay combination index and cytotoxicity assessed by MTT assays. Apoptosis was measured through caspase-3/7 activity, and transcriptional changes in H19 lncRNA, P53, Bax, and Bcl-2 were quantified by real-time PCR. Silibinin and paclitaxel exhibited a synergistic effect, reducing paclitaxel IC50 and increasing cytotoxicity. Co-treatment enhanced caspase-3/7 activation, upregulated pro-apoptotic P53 and Bax, and downregulated anti-apoptotic Bcl-2 and oncogenic H19 lncRNA. Silibinin alone caused a threefold reduction in H19 expression, whereas paclitaxel alone had minimal effect. Silibinin potentiates paclitaxel cytotoxicity by suppressing H19 transcription, offering a potential strategy to overcome paclitaxel resistance. The combination promotes apoptosis via caspase activation, highlighting a novel synergistic therapeutic approach in breast cancer treatment.