Reversing ABCB1-Mediated Multidrug Resistance in Colorectal Cancer: electroacupuncture shows therapeutic potential <i>in vivo</i>

Objectives: ATP-binding cassette sub-family B member 1 (ABCB1) is closely associated with multidrug resistance (MDR) in colorectal cancer; however, safe and effective clinical treatment options remain limited. This study aimed to evaluate electroacupuncture, a traditional Chinese medicine technique, for its potential to overcome ABCB1-mediated MDR in colorectal cancer and investigate the underlying mechanisms. Methods : The tumor-inhibitory effects of electroacupuncture were investigated in nude mice with ABCB1 overexpression-induced MDR. Chemotherapy drug metabolism in tumor tissues and blood was assessed using pharmacokinetic analysis. In vivo fluorescence imaging was employed to monitor the accumulation of the ABCB1 substrate Rhodamine 123 within tumors. ABCB1 expression was analyzed using Western blotting, polymerase chain reaction (PCR), and immunofluorescence. Proteomic and bioinformatic analyses were conducted to explore the mechanisms through which electroacupuncture overcomes ABCB1-mediated drug resistance. Results : Electroacupuncture significantly enhanced the sensitivity of ABCB1-mediated MDR nude mice to paclitaxel, markedly inhibiting tumor growth and promoting apoptosis. Tumor drug concentrations increased, while the expression of hypoxia-inducible factor 1-alpha (HIF1A) and its downstream target, ABCB1, decreased. Proteomic analyses suggested that extracellular matrix (ECM) remodeling plays a key role, indicated by decreased TIMP-1 and increased collagen expressions (collagen alpha-1(I) chain [COL1A1], collagen alpha-2(I) chain [COL1A2], and collagen alpha-1 (XVIII) chain [COL18A1]). Collectively, these findings indicate that electroacupuncture may influence tumor mechanical properties and the hypoxic microenvironment by modulating the balance between ECM degradation and deposition, providing a potential mechanistic explanation for the reversal of ABCB1-mediated MDR. Conclusion : Electroacupuncture may reverse ABCB1-mediated tumor MDR, potentially through ECM remodeling and improvement of the tumor mechanical microenvironment. These insights provide a basis for developing new strategies to combat clinical drug resistance.