The anthelmintic agent oxfendazole inhibits cell growth in non‑small cell lung cancer by suppressing c‑Src activation

Mol Med Rep. 2019 Apr;19(4):2921-2926. doi: 10.3892/mmr.2019.9897. Epub 2019 Jan 28.

Abstract

The c‑Src protein family of tyrosine kinases are important in the tumorigenesis of many types of tumors, and may be a potential target for antitumor drug discovery. In the present study, immunoblotting was performed to analyze protein expression, CCK‑8 assay was carried out to assess cell viability and cell cycle was analyzed using a flow cytometer. The anthelmintic agent oxfendazole was observed to be a novel c‑Src inhibitor that blocked the activation of c‑Src. Oxfendazole also suppressed the cell growth of non‑small cell lung cancer (NSCLC) cells, and overexpression of c‑Src decreased the cytotoxicity of oxfendazole against NSCLC cells. In addition, oxfendazole induced cell cycle arrest at the G0/G1 phase, and downregulated the protein levels of Cyclin‑dependent kinase (CDK)‑4, CDK6, retinoblastoma protein and E2 transcription factor 1, and upregulated the expression levels of p53 and p21 in NSCLC cells. Furthermore, oxfendazole enhanced the cytotoxicity of cisplatin against NSCLC cells. These results demonstrated that oxfendazole exerted its antitumor activity by suppressing c‑Src signaling, and it was also indicated that the anthelmintic agent oxfendazole may be effective for anti‑NSCLC therapy in the clinic as a single agent or in combination with other antitumor drugs.

MeSH terms

  • Apoptosis / drug effects
  • Benzimidazoles / pharmacology*
  • CSK Tyrosine-Protein Kinase
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation
  • Cisplatin / pharmacology
  • Enzyme Activation / drug effects
  • Humans
  • Lung Neoplasms / metabolism*
  • Protein Kinase Inhibitors / pharmacology*
  • Signal Transduction / drug effects
  • src-Family Kinases / antagonists & inhibitors*
  • src-Family Kinases / metabolism

Substances

  • Benzimidazoles
  • Protein Kinase Inhibitors
  • CSK Tyrosine-Protein Kinase
  • src-Family Kinases
  • CSK protein, human
  • oxfendazole
  • Cisplatin