Shikonin inhibits growth, invasion and glycolysis of nasopharyngeal carcinoma cells through inactivating the phosphatidylinositol 3 kinase/AKT signal pathway.

Abstract

Nasopharyngeal carcinoma (NPC) is a malignant tumor which is commonly found in East Asia and Africa. The present clinical treatment of NPC is still mainly based on chemotherapeutics and is prone to drug resistance and adverse reactions. Shikonin has been demonstrated to play the antitumor effect in various cancers. However, the specific effects and related regulatory mechanism of Shikonin in NPC have not been clearly declared yet. Cell viability was valued through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cell proliferation was detected through colony formation assay and Bromodeoxyuridine (BrdU) assay. Hochest 33258 staining was used to value cell apoptosis. Cell migration and invasion were valued through wound healing and transwell invasion assay, respectively. Glucose uptake, lactate release, ATP level and pyruvate kinase M2 isoform (PKM2) activity were measured using corresponding assay kits. Western blotting was used to examine the expression of proteins related to cell proliferation, cell apoptosis, cell migration and the phosphatidylinositol 3 kinase (PI3K)/AKT signal pathway. We found that Shikonin treatment effectively suppressed cell proliferation and induced obvious cell apoptosis compared with the control. Besides, Shikonin treatment suppressed cell migration and invasion effectively. The detection about glycolysis showed that Shikonin treatment suppressed cell glucose uptake, lactate release and ATP level. The activity of PKM2 was also largely inhibited by Shikonin. Further study revealed that the PI3K/AKT signal pathway was inactivated by Shikonin treatment. In addition, the inducer of the PI3K/AKT signal pathway largely abolished the antitumor effect of Shikonin on cell proliferation, cell apoptosis, cell mobility and aerobic glycolysis in NPC cells. Shikonin inhibits growth and invasion of NPC cells through inactivating the PI3K/AKT signal pathway.