Vinpocetine Overcomes Paclitaxel Resistance in a Triple-Negative Breast Cancer Cell Line

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Paclitaxel is a key treatment for triple-negative breast cancer (TNBC).
• Tumor-cell resistance frequently limits paclitaxel efficacy in TNBC.
• Vinpocetine is a dietary supplement with potential anti-cancer properties.

Purpose of the Study:

• To investigate if vinpocetine can enhance the sensitivity of TNBC cells to paclitaxel.
• To elucidate the mechanisms by which vinpocetine might overcome paclitaxel resistance.

Main Methods:

• Established a paclitaxel-resistant TNBC cell line (T50RN) from MDA-MB-231 cells.
• Assessed the effects of vinpocetine on T50RN cell sensitivity to paclitaxel.
• Investigated the roles of PDE1C and P-gp in vinpocetine's action.

Main Results:

• Vinpocetine significantly enhanced paclitaxel sensitivity in resistant T50RN cells.
• Overexpression of PDE1C contributed to paclitaxel resistance; vinpocetine's effects were partly independent of PDE1C.
• Vinpocetine disrupted P-gp function, increasing paclitaxel accumulation and efficacy.
• Vinpocetine enhanced paclitaxel-induced microtubule stabilization.

Conclusions:

• Vinpocetine overcomes paclitaxel resistance in TNBC cells through multiple mechanisms.
• Targeting both PDE1C and P-gp by vinpocetine enhances paclitaxel's antimitotic effects.
• Vinpocetine shows promise as an adjuvant therapy to improve paclitaxel treatment outcomes in TNBC.