Polyphyllin H Reverses Paclitaxel Resistance in Breast Cancer by Binding Membrane Cholesterol to Inhibit Both ABCB1 and ABCC3.

ABSTRACT: Background/Objectives: Breast cancer is the most prevalent malignancy among women, and paclitaxel (PTX) is a first-line chemotherapeutic, but chemoresistance driven by ATP-binding cassette (ABC) transporters limits its efficacy. Single-target ABC inhibitors fail due to toxicity and cooperative transporter activity, creating an urgent need for safe multi-target strategies. Membrane cholesterol-rich lipid rafts support ABC transporter function, making cholesterol a key chemoresistance target. This study explored a cholesterol-targeted approach for overcoming PTX resistance. Methods: A PTX-resistant breast cancer line (MCF-7/PTX) showing ABCB1/ABCC3 co-upregulation and enriched cholesterol rafts was established. The effects of Polyphyllin H (PPH), a steroidal saponin from Par

SUBMITTER: Ye Z 

PROVIDER: S-EPMC12655514 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature