Targeting NFAT2 for Reversing the P-gp-Mediated Multidrug Resistance to Paclitaxel by Manidipine.

ABSTRACT:

Background

Multidrug resistance (MDR), primarily driven by P-glycoprotein (P-gp)-mediated drug efflux, presents a significant challenge in cancer therapy, contributing to chemotherapy failure and poor patient outcomes.

Objectives

In this study, we explored the potential of manidipine (MA), a clinically approved calcium channel blocker, to reverse P-gp-mediated MDR through modulation of calcium signaling via nuclear factor of activated T cells 2 (NFAT2).

Methods

Paclitaxel (PTX) resistance ABCB1-overexpressing cancer in vitro and in vivo were used for evualting the anti-MDR effects of MA, as well as the underlying mechanism with siRNA of NFAT2.

Results

We found that MA at non-toxic concentrations (0.6-5.4 μM) significantly sensitize drug-resistant colorectal (HC

SUBMITTER: Zhou J 

PROVIDER: S-EPMC12562668 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature