Apatinib Reverses Paclitaxel-resistant Lung Cancer Cells (A549) Through Blocking the Function of ABCB1 Transporter

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Multidrug resistance (MDR) in cancer is frequently linked to P-glycoprotein (ABCB1) overexpression.
• Apatinib, a VEGFR-TKI, shows potential in inhibiting ABCB1 function in specific cancer types.
• Paclitaxel (PTX) resistance in A549 lung cancer cells (A549/PTX) is a significant clinical challenge.

Purpose of the Study:

• To investigate the efficacy of apatinib in reversing paclitaxel resistance in A549/PTX cells.
• To elucidate the underlying mechanisms by which apatinib affects PTX resistance.
• To evaluate the combined effects of apatinib and PTX on resistant lung cancer cells.

Main Methods:

• A549/PTX cells were treated with apatinib, PTX, or a combination.
• Cell viability (CCK8 assay), apoptosis, cell cycle, Rhodamine efflux, and ROS generation were assessed via flow cytometry.
• Intracellular PTX levels were quantified using UPLC, and protein expressions were analyzed by western blotting.

Main Results:

• Apatinib treatment significantly increased PTX cytotoxicity and apoptosis in A549/PTX cells.
• Apatinib enhanced intracellular paclitaxel concentration and induced ROS generation.
• The combination therapy inhibited AKT and ERK signaling pathways.
• Apatinib treatment led to increased ABCB1 inhibition, reversing PTX resistance.

Conclusions:

• Apatinib effectively reverses paclitaxel resistance in A549 PTX-resistant lung cancer cells.
• Inhibition of ABCB1 function by apatinib is a key mechanism in overcoming MDR.
• Apatinib restores the anti-cancer efficacy of paclitaxel in resistant lung cancer models.