Lidocaine inhibits the proliferation and invasion of hepatocellular carcinoma by downregulating USP14 induced PI3K/Akt pathway

Abstract Previous studies have found that Lidocaine (Lido) has marked anti-tumor effects. The purpose of this study was to explore the effect and mechanism of Lido on hepatocellular carcinoma (HCC). Here, the Huh-7 and SMMC-7721 HCC cells were treated with Lido, then the proliferation, migration and invasion of HCC cells were detected by CCK8, wounding healing assay and Transwell assay. Besides, apoptotic proteins (including Caspase3 and Bcl2), epithelial-mesenchymal transition (EMT) associated markers (including E-cadherin and Vimentin), USP14, PI3K/Akt pathway were detected by western blot. Our results revealed that Lido significantly inhibited the proliferation, migration and invasion while aggravate the apoptosis of HCC cells, as well as the expression of USP14 and the activation of PI3K/Akt. Loss-of-function experiments confirmed that USP14 downregulation attenuated the malignant behaviors of HCC cells through repressing PI3K/Akt signaling pathway. Mechanistically, USP14 functioned by deubiquitinating and activating PI3K. In conclusion, Lido inhibits the proliferation and metastasis of HCC cells by targeting USP14 and its downstream PI3K/Akt signaling pathway.