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Reversing ABCB1-Mediated Multidrug Resistance in Colorectal Cancer: electroacupuncture shows therapeutic potential in
Yuqin Qiu1, Zhenjia Fan2, Xuewei Qi3
1Department of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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.
Insights
Electroacupuncture reverses multidrug resistance (MDR) in colorectal cancer by improving tumor drug delivery and reducing ABCB1 expression. This traditional Chinese medicine technique offers a novel strategy to overcome treatment resistance.
Area of Science:
- Oncology
- Traditional Chinese Medicine
- Molecular Biology
Background:
- ATP-binding cassette sub-family B member 1 (ABCB1) overexpression drives multidrug resistance (MDR) in colorectal cancer, limiting treatment efficacy.
- Current therapeutic options for ABCB1-mediated MDR in colorectal cancer are insufficient.
Purpose of the Study:
- To evaluate the efficacy of electroacupuncture in overcoming ABCB1-mediated MDR in colorectal cancer.
- To elucidate the underlying mechanisms by which electroacupuncture reverses MDR.
Main Methods:
- Investigated electroacupuncture's tumor-inhibitory effects in MDR colorectal cancer xenografts.
- Assessed chemotherapy drug pharmacokinetics, Rhodamine 123 accumulation via in vivo imaging, and ABCB1 expression (Western blot, PCR, immunofluorescence).
- Utilized proteomic and bioinformatic analyses to explore resistance reversal mechanisms.
Main Results:
- Electroacupuncture significantly enhanced paclitaxel sensitivity, inhibited tumor growth, and promoted apoptosis in MDR models.
- Reduced expression of hypoxia-inducible factor 1-alpha (HIF1A) and ABCB1 was observed.
- Proteomics indicated extracellular matrix (ECM) remodeling, with altered TIMP-1, COL1A1, COL1A2, and COL18A1 expression, suggesting modulation of tumor mechanical properties and the hypoxic microenvironment.
Conclusions:
- Electroacupuncture demonstrates potential in reversing ABCB1-mediated MDR in colorectal cancer.
- ECM remodeling and improved tumor mechanical microenvironment are proposed mechanisms.
- Findings support electroacupuncture as a strategy to combat clinical drug resistance.
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