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

• Published in: Molecular medicine reports Vol. 19; no. 4; pp. 2921 - 2926
• Main Authors: Xu, Dafu, Tian, Wenze, Jiang, Chao, Huang, Ziming, Zheng, Shiying
• Format: Journal Article
• Language: English
• Published: Greece Spandidos Publications 01.04.2019; Spandidos Publications UK Ltd
• Subjects: Angiogenesis; Anthelmintic agents; Antitumor activity; Biotechnology; c-Src protein; Cancer; Cancer therapies; Carbamates; Cell adhesion & migration; Cell cycle; Cell growth; Cell viability; Chemotherapy; Cholecystokinin; Cisplatin; Cyclin-dependent kinase; Cyclin-dependent kinases; Cytotoxicity; Drug discovery; Drugs; Epidermal growth factor; G1 phase; Gene expression; Genetic aspects; Immunoblotting; Immunoglobulins; Kinases; Laboratories; Lung cancer; Non-small cell lung cancer; Non-small cell lung carcinoma; Novels; Oxfendazole; p53 Protein; Phenols (Class of compounds); Plasmids; Proteins; Retina; Retinoblastoma; Retinoblastoma protein; Small cell lung cancer; Src protein; Statistical analysis; Tumor proteins; Tumorigenesis; Tumors; Tyrosine; Beijing China; United States > US; China
• ISSN: 1791-2997; 1791-3004
• DOI: 10.3892/mmr.2019.9897

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.