Cantharidic acid inhibits the malignant progression of colorectal cancer by inhibiting aerobic glycolysis and regulating the PI3K/Akt/P53 pathway.

Cantharidic acid (CA) has shown effective anticancer activity against many solid tumor cells, but it has not been reported in colorectal cancer (CRC). The PFKFB3 overexpression vector was transfected into SW480 and HT29 cells and the cells were treated with CA and PI3K activator 740 Y-P for 24 h. The malignant progression of the cells was evaluated through CCK-8, EdU, Transwell, flow cytometry, LDH release assay and Hoechst 33258 fluorescence. The expressions of aerobic glycolysis (AEG) and PI3K/Akt/P53 pathway were detected using the kit, extracellular acidification rate (ECAR) assay and Western blot. The subcutaneous tumor model was established by subcutaneous injection of SW480 cells. CA could significantly reduce the proliferation, migration and invasion of SW480 and HT29 cells and promote apoptosis and trigger cell cycle arrest. CA could reduce glucose uptake, lactic acid production and glycolytic capacity, reduce p-PI3K and p-Akt protein levels, raise P53 protein level. PFKFB3 overexpressed promoted CRC malignant progression. 740 Y-P could increase the AEG of CRC cells. Finally, CA reduced the volume and weight of CRC xenografts in mice and inhibited AEG and malignant biological behavior. In conclusion, CA inhibited AEG and malignant progression of CRC cells by regulating the PI3K/Akt/P53 pathway.