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Vinpocetine is a well\u2010tolerated dietary supplement with pleiotropic cellular effects, including potential anti\u2010tumor activity. In this study, we tested whether and how vinpocetine might enhance the sensitivity of TNBC cells to paclitaxel. A paclitaxel\u2010resistant TNBC cell line (T50RN) was established by incubating MDA\u2010MB\u2010231 cells with escalating concentrations of paclitaxel (0.5\u201350\u2009nM). The effects of vinpocetine on T50RN cell sensitivity to paclitaxel were examined. T50RN cells were significantly more resistant to paclitaxel than the parental MDA\u2010MB\u2010231 cells. Vinpocetine itself was slightly cytotoxic to cells but considerably enhanced paclitaxel sensitivity in T50RN cells. Expression of PDE1C, a target of vinpocetine, was elevated in T50RN cells. Depletion of PDE1C moderately enhanced paclitaxel sensitivity of T50RN cells, suggesting that PDE1C overexpression might contribute to paclitaxel resistance. In addition, vinpocetine induced microtubule stabilization and significantly enhanced paclitaxel\u2010induced microtubule stabilization. However, vinpocetine could still enhance paclitaxel sensitivity in PDE1C\u2010depleted T50RN cells, indicating that vinpocetine also acts through factor(s) other than PDE1C. P\u2010gp expression and activity were elevated in T50RN cells, and inhibition of P\u2010gp sensitized T50RN cells to paclitaxel. Vinpocetine functionally disrupted P\u2010gp in T50RN cells and further enhanced the death of P\u2010gp\u2010inhibited paclitaxel\u2010treated T50RN cells. Thus, our results revealed that vinpocetine may act on P\u2010gp and PDE1C to facilitate paclitaxel accumulation and paclitaxel\u2010induced stabilization of microtubules in T50RN cells, thereby enhancing the antimitotic effects of paclitaxel and disrupting paclitaxel\u2010resistance mechanisms.<\/jats:p>","DOI":"10.1002\/cbin.70088","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T12:48:04Z","timestamp":1759236484000},"page":"1716-1729","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Vinpocetine Overcomes Paclitaxel Resistance in a Triple\u2010Negative Breast Cancer Cell Line"],"prefix":"10.1002","volume":"49","author":[{"given":"Hsiao\u2010Hui","family":"Kuo","sequence":"first","affiliation":[{"name":"Institute of Cellular and Organismic Biology Academia Sinica Taipei 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