Moxibustion enhances the antitumor efficacy of Trametinib in breast cancer-bearing mice via MEK/ERK signaling pathway

ObjectiveTo explore the synergistic inhibitory effect of moxibustion and mitogen-activated protein kinase kinase （MEK）/ extracellular regulated protein kinases （ERK） pathway inhibitor Trametinib on tumor growth in breast cancer tumor-bearing mice and to analyze its underlying mechanisms.MethodsFifty female BALB/C mice were randomly divided into blank control， model， inhibitor （Trametinib）， direct moxibustion and combination （Trametinib+moxibustion） groups， with 10 mice in each group. Injection of 4T1 cells was used to establish breast cancer tumor-bearing mouse model. Both the blank control and model groups received gavage of 0.1 mL of normal saline once daily. In the inhibitor group， Trametinib solution was administered by gastric gavage at 3 mg/kg， once a day for 21 d. For mice of the direct moxibustion group， moxibustion was applied at bilateral “Zusanli” （ST36）， 2 cones per acupoint， once every 2 days for 21 d. The combination group was treated with administration of Trametinib （once daily） by gastric gavage and direct moxibustion （once every 2 d） for 21 d. Body weight and tumor volumes were measured in mice. The tumor weight was quantified and the tumor inhibition rate was calculated. Histopathological alterations in tumor tissues were observed after H.E. staining. The protein expression levels of phosphorylated （p）-MEK， p-ERK， myelocytomatosis viral oncogene homolog （c-Myc）， and programmed cell death ligand 1 （PD-L1） in the tumor tissues were assessed using immunohistochemical staining and Western blot， separately. Additionally， the mRNA expression levels of c-Myc and PD-L1 in the tumor tissue were detected using fluorescence quantitative real-time PCR.ResultsAfter the intervention， compared with the blank control group， the body mass of mice was decreased evidently in both the model and inhibitor groups （PPPPPPPPPPPConclusionMoxibustion can enhance the anti-tumor effect of Trametinib by inhibiting the phosphorylation of MEK/ERK pathway and the downstream c-Myc/PD-L1 axis in mice with breast cancer， which provides an experimental basis for the adjuvant targeting therapy of breast cancer with moxibustion.