Actinidia Chinensis Root Extract Inhibits the Proliferation, Migration, Invasion and Glycolysis of Breast Cancer Cells Through the Akt-mTOR Mediated Autophagy Signaling Pathway

OBJECTIVE To investigate the effects of the Actinidia chinensis root extract(acRoots) on the proliferation, migration, invasion and glycolysis of breast cancer cells MDA-MB-231. METHODS MTT assay and clony formation assay were used to detect the proliferation ability of MDA-MB-231 cells treated with acRoots extract. The wound healing and Transwell asssays were performed to detect cell migration and invasion. Western blotting was used to detect the protein levels of matrix metalloproteinase 2(MMP-2) and matrix metalloproteinase 9(MMP-9). Glucose uptake kit and lactate colorimetry kit were used to detect glucose intake and lactate production in cells. Western blotting was used to detect the expression of the level of glycolysis-related proteins pyruvate kinase M2(PKM2), glucose transporter1(GLUT1), lactate dehydrogenase A(LDHA) and Akt-mTOR mediated autophagy signaling pathway. RESULTS Compared with the control group, the acRoots extract (10 mg·mL^-1) could significantly inhibit the cell viability of MDA-MB-231 cells, while the cell activity of MDA-MB-231 cells was not affected by 0.1 and 1 mg·mL^-1 acRoots extract. The acRoots extract could significantly reduce the colony formation, migration rate, number of invasion cells, glucose uptake and lactic acid production of MDA-MB-231 cells in a dose-dependent manner(all P<0.05). The extract of acRoots(1 μg·mL^-1 and 10 μg·mL^-1) could reduce the expression of cell migration marker proteins(MMP-2 and MMP-9), and inhibit the expression of glycolysis-related proteins PKM2, GLUT1 and LDHA(all P<0.05). In addition, the extract of acRoots inhibited the activity of key proteins in the Akt/mTOR signaling pathway, decreased the expression of p-Akt and p-mTOR, promoted the conversion of LC3Ⅰ to LC3Ⅱ, up-regulated the autophagy-related protein Beclin1, down-regulated the autophagic marker protein p62, enhanced MDA-MB-231 cell autophagy activity(all P<0.05). CONCLUSION The acRoots extract inhibit cell proliferation, migration, invasion and glycolysis, and its effect may be related to autophagy induced by inactivating Akt-mTOR pathway.