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Peritumor electroacupuncture facilitates vascular normalization


Recent therapeutic strategies for the treatment of triple-negative breast cancer (TNBC) have shifted the focus from vascular growth factors to endothelial cell metabolism. This study highlights the underexplored therapeutic potential of peri-tumoral electroacupuncture, a globally accepted non-pharmacological intervention for TNBC, and molecular mechanisms.

Recent studies have shown that acupuncture may exert certain inhibitory effects on the growth of breast cancer and osteosarcoma. Electroacupuncture represents an advanced modification of traditional acupuncture, designed to meet the requirements of standardization in clinical practices and scientific researches. This innovative approach synergizes the conventional methodology of needle insertion at specific acupoints with the application of controlled electrical stimulation. Our previous study found that peri-tumor acupuncture intervention could effectively reduce the local microvascular density of 4T1 breast cancer and increase the concentration of paclitaxel in the transplanted tumor 2 h post-intervention.


For electroacupuncture interventions, sterile acupuncture needles (size 0.18 × 15 mm, Suzhou DongBang Medical Co., Ltd., Suzhou, China) were used. As previously described [29], four needles were inserted toward the tumor in the up, down, left, and right directions in tumor-bearing mice under anesthesia. The acupuncture site was around 5 mm off the boundary of the tumor in tumor-bearing mice or the left thigh in control mice, and an acupuncture depth was around 5 mm (Fig. 1A). Electroacupuncture interventions were performed using an SDZ-V electronic acupuncture treatment device (Hwato Co., Suzhou, China). The device was set to deliver a longitudinal wave alternating between low frequency (3–4 Hz for 5 s) and high frequency (15–20 Hz for 10 s). The intensity was adjusted to induce moderate hindlimb muscle contraction (3 mA).


From T1 (1 day after acupuncture) to T7 (7 days after acupuncture), the TG group (Tumor-bearing model group without treatment) showed relatively stable microvascular photoacoustic signals in the tumor region, and these signals were mostly distributed in scattered clusters. The EATG group (Tumor-bearing mice + electroacupuncture) showed a trend of decreasing and then increasing microvascular photoacoustic signals in the tumor region from T1 to T7, while the BTG group (Tumor-bearing mice + bevacizumab) exhibited a similar trend to the EATG group (Fig. 1B). Observation of the photoacoustic signal images from the sagittal plane of the tumor revealed that scattered, cluster-like blood vessel signals decreased, while linear, regular blood vessel signals increased following electroacupuncture intervention.

Electroacupuncture combined with paclitaxel chemotherapy administered within the vascular normalization time window (3 days after electroacupuncture, EA3PTG) showed a significant inhibition of tumor growth. This combination therapy was superior to the group receiving acupuncture and chemotherapy outside the optimal intervention window (paclitaxel given 1 day after acupuncture, EA1PTG). The difference in tumor growth inhibition between the two groups was statistically significant (P < 0.001). In contrast, tumor growth in the EA1PTG group was not significantly different from that of the group receiving paclitaxel chemotherapy alone (PTG). In addition, the tumor inhibition rate of the EA3PTG group was 55.03 %.

 Multi-omics analysis revealed Glyoxalase 1 (Glo1) and the associated methylglyoxal-glycolytic pathway as key mediators of electroacupuncture-induced vascular normalization. Peri-tumoral electroacupuncture notably reduced Glo1 expression in the endothelial cells of 4T1 xenografts. Using an in vivo matrigel plug angiogenesis assay, it was shown that either Glo1 knockdown or electroacupuncture inhibited angiogenesis. In contrast, Glo1 overexpression increased blood vessel formation. In vitro pharmacological inhibition and genetic knockdown of Glo1 in human umbilical vein endothelial cells inhibited proliferation and promoted apoptosis via downregulating the methylglyoxal-glycolytic pathway. The study using the Glo1-silenced zebrafish model further supported the role of Glo1 in vascular development.


This study underscores the pivotal role of Glo1 in peri-tumoral electroacupuncture, spotlighting a promising avenue for enhancing vascular normalization and improving TNBC treatment outcomes.

My comments:

The acupuncture used here is peritumor electroacupuncture, not classical acupuncture. We offer the peritumor electroacupuncture service. This manuscript showed clearly that acupuncture can not only be used to assist conventional medicine to deal with side effects, but also can work on the tumor itself.


Yu-Xiang Wan, Xue-Wei Qi, Yan-Yan Lian, Ze-Yu Liu, Hui Wang, Yu-Qin Qiu, Chun-Guang Zhang, Wen-Na Li, Hong-Lin Jiang, Dong-Hua Yang, Wei Zhao, Zhe-Sheng Chen, Jin-Chang Huang. Electroacupuncture facilitates vascular normalization by inhibiting Glyoxalase1 in endothelial cells to attenuate glycolysis and angiogenesis in triple-negative breast cancer. Cancer Lett. 2024 Jun 29:598:217094. doi: 10.1016/j.canlet.2024.217094.

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