Gastrodin overcomes chemoresistance via inhibiting Skp2-mediated glycolysis
Aerobic glycolysis, an average phenotype in human tumors, is connected with tumor progression and chemotherapy resistance. The current study shown that cisplatin-resistant dental squamous cell carcinoma (OSCC) cells exerted a more powerful glycolysis ability, that was connected with hexokinase 2 (HK2) overexpression. Furthermore, the tumor development of OSCC cells was delayed in vivo and also the glycolysis was particularly decreased following HK2 knockdown. Natural compound screening says gastrodin happens to be an effective candidate for OSCC therapy because it inhibited HK2-mediated glucose metabolic process and promoted endogenous OSCC cell apoptosis. In addition, gastrodin could bind to protein kinase B (Akt) and suppress its activity, thus downregulating HK2 in the transcriptional level. Furthermore, S-phase kinase-connected protein 2 (Skp2) was highly expressed in OSCC cells, while K63-linked ubiquitination of Akt was inhibited in Skp2-depleted cisplatin-resistant OSCC cells. Gastrodin may also hinder the cisplatin resistance of OSCC cells in vivo, specially when combined with Skp2 inhibitor, SZL P1-41. Overall, SZL P1-41 these finding recommended that individuals Skp2-Akt axis might be a potential therapeutic technique for treating OSCC and overcoming chemoresistance.