Effect of moxibustion combined with cisplatin on tumor microenvironment hypoxia and vascular normalization in Lewis lung cancer mice

Abstract Purpose This study was developed to evaluate the effects of moxibustion on tumor microenvironmental hypoxia in a murine model of Lewis lung carcinoma (LLC). Methods In total, 30 female C57BL/6 mice were randomized into tumor (T), moxibustion (TM), chemotherapy (TC), and moxibustion + chemotherapy (TMC) groups (n = 6/group). A tumor model was established by implanting LLC cells into the right flank of each mouse. Animals in the TM group were subjected to moxibustion treatment at the ST36 (bilateral) and GV4 acupoints on the day after visible tumor formation (8 days after tumor injection). Moxibustion treatment was repeated every other day for 7 total treatments. Animals in the TC group were intraperitoneally injected with cisplatin (3 mg/kg) on day 3 after visible tumor formation (day 10 after modeling), and this treatment was repeated every 3 days for 4 total treatments. Animals in the TMC group underwent a combination of moxibustion and chemotherapy using the same conditions outlined above. After treatment was complete, ELISAs were used to measure serum concentrations of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and CD31, while the levels of the former three of these factors were assessed in tumor tissue samples via Western immunoblotting and immunohistochemical staining. Results Relative to the T model group, treatment in the TM, TC, and TCM groups resulted in varying reductions in tumor growth (P < 0.001 or P < 0.05), while tumor microenvironmental hypoxia was alleviated as evidenced by the downregulation of HIF-1α, VEGFA, and CD31(P < 0.001 ~ P < 0.05). Conclusion The combination of moxibustion and cisplatin can alleviate intratumoral hypoxia, promote vascular normalization and slow LLC tumor growth in mice.