Anlotinib Suppresses Oral Squamous Cell Carcinoma Growth and Metastasis by Targeting the RAS Protein to Inhibit the PI3K/Akt Signalling Pathway

Anal Cell Pathol (Amst). 2021 Dec 8:2021:5228713. doi: 10.1155/2021/5228713. eCollection 2021.

Abstract

Oral squamous cell carcinoma (OSCC) is a malignant tumour originating from the mucosal lining of the oral cavity. Its characteristics include hidden onset, high recurrence, and distant metastasis after operation. At present, clinical treatment usually includes surgery, chemotherapy, radiotherapy, or the joint use of these modalities. Unfortunately, multidrug resistant is one of the important obstacles that causes cancer chemotherapy failure. Anlotinib, which has recently been proven to have good antitumour effects, is a novel multitargeted tyrosine kinase inhibitor. However, there are few studies of the anlotinib-associated mechanism in OSCC and its underlying molecular mechanism. In our study, in vitro models of human oral squamous cell carcinoma HSC-3 cells were used to determine the efficacy of anlotinib. On the one hand, we showed that anlotinib treatment significantly reduced the viability and proliferation of HSC-3 cells and decreased cell migration by inhibiting the activation of the Akt phosphorylation pathway. On the other side, anlotinib inhibited PI3K/Akt/Bad phosphorylation and promoted apoptosis of HSC-3 cells by activating RAS protein expression. In brief, these results indicated that anlotinib had prominent antitumour activity in OSCC, mainly by inhibiting the PI3K/Akt phosphorylation pathway. This work provides evidences and a basic principle for using anlotinib to treat patients with OSCC for clinical research.

MeSH terms

  • Apoptosis / drug effects
  • Blotting, Western
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Humans
  • Indoles / pharmacology*
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / pathology
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Quinolines / pharmacology*
  • Signal Transduction / drug effects*
  • ras Proteins / antagonists & inhibitors*
  • ras Proteins / metabolism

Substances

  • Indoles
  • Quinolines
  • anlotinib
  • Proto-Oncogene Proteins c-akt
  • ras Proteins