Ornidazole Inhibits the Angiogenesis and Migration Abilities of Non-small Cell Lung Cancer (NSCLC) via Downregulation of VEGFA/VEGFR2/NRP-1 and PI3K/AKT/mTOR Pathways.

BACKGROUND

Around the world, non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths among all cancers. Despite advancements in new therapeutic approaches over the past few decades, the five-year survival rate still remains disappointing. The lack of effective anti-angiogenic and anti-migration drugs is the biggest obstacle to the treatment of metastatic lung cancer. Therefore, there is a need to develop new and effective therapeutic compounds targeting anti-angiogenic and anti-migration pathways for the treatment of lung cancer. Ornidazole is a nitroimidazole agent widely used in the treatment of parasitic infections such as trichomonas vaginalis, amebiasis and giardiasis. This study aimed to investigate the anti-proliferative, anti-angiogenic and anti-mitotic activities of the anti-parasitic drug Ornidazole in two human lung cancer cell lines (A549, H1299).

METHODS

We determined the effects of Ornidazole, on cell viability, apoptosis, migration, angiogenesis and metastatic ability against NSCLC in lung cancer cell lines. Its action on the mRNA and protein expression levels of VEGFA, VEGFR2, NRP1, Casp9, Casp3, Bax, Bcl-2, PIK3CA, AKT, MTOR, PTEN and FOX3A was assessed. Furthermore, in this study the effects on cell migration, cell viability and proliferation was evaluated through wound healing, MTT and Crystal violet assays.

RESULTS

This study demonstrated that Ornidazole effectively reduces cell viability and migration ability, inhibits angiogenesis and metastatic abilities in NSCLC cells.

CONCLUSIONS

In conclusion, these results may shed light on the treatment of NSCLC, and we suggest the anti-parasitic drug Ornidazole as a new agent with potential anti-angiogenic and anti-mitotic activity by interfering with the molecular pathways that trigger tumor angiogenesis and migration.