[The role of peritumoral electroacupuncture in regulating cuproptosis for sensitization of chemotherapy efficacy in mice with triple-negative breast cancer].

OBJECTIVES

To explore the enhanced sensitization effect of peritumoral electroacupuncture (PEA) on doxorubicin (DOX) chemotherapy in mice with triple-negative breast cancer (TNBC).

METHODS

Eighteen female Balb/c mice were randomly divided into the model, DOX, and EA+DOX groups, with 6 mice in each group. TNBC cells were injected into the mammary fat pad of mice to establish the breast cancer-bearing mice model. Mice of the DOX and EA+DOX groups were injected intraperitoneally with DOX solution at 4 mg/kg once a week for 4 weeks. For mice of the EA+DOX group, 4 filiform needles were inserted surrounding tumor tissues, followed by giving the mice with EA (1 mA, 2 Hz/100 Hz) stimulation for 3 min, once a week for 4 weeks. During the intervention, the tumor volume was measured every two days, and at the end of intervention, the weight of the tumor tissue was measured. The expression of Ki67 and proliferating cell nuclear antigen (PCNA) in tumor tissues was detected by immunohistochemistry. The protein expression levels of iron redox protein 1 (FDX1), lipoic acid synthase (LIAS), aconitase 2 (ACO2) and NADH：ubiquinone oxidoreductase core subunit V1 (NDUFV1), dihydrolipoamide S-acetyltransferase(DLAT), dihydrolipoyl succinyltransferase(DLST) in tumor tissues were detected by Western blot. The content of copper ions, pyruvic acid and α-ketoglutaric acid, succinic acid in tumor tissues was detected by copper ion kit, and the content of reactive oxygen species (ROS) in tumor tissues of mice was detected by fluorescence method.

RESULTS

Compared with the model group, the tumor volume and weight, the expression levels of Ki67 and PCNA in tumor tissues were decreased (<0.05, <0.01) in the DOX and EA+DOX groups. The improvement of the above indicators was more significant in the EA+DOX group than that in the DOX group (<0.05, <0.01). Compared with the model and DOX groups, the contents of ROS, copper ions, pyruvic acid and α-ketoglutaric acid were increased (<0.05, <0.01), while the contents of succinic acid, and the expressions of FDX1, LIAS, ACO2 and NDUFV1, DLAT, DLST proteins were decreased (<0.01) in the EA+DOX group.

CONCLUSIONS

The combination of PEA and DOX can effectively control the growth rate of tumors in mice with TNBC, which may contribute to its function in enhancing the chemotherapy efficacy of DOX on TNBC by promoting cuproptosis.