Albendazole inhibits HIF-1α-dependent glycolysis and VEGF expression in non-small cell lung cancer cells
- 372 Downloads
Albendazole (ABZ) has an anti-tumor ability and inhibits HIF-1α activity. HIF-1α is associated with glycolysis and vascular endothelial cell growth factor (VEGF) expression, which plays an important role in cancer progression. These clues indicate that ABZ exerts an anti-cancer effect by regulating glycolysis and VEGF expression. The aim of this study is to clarify the effects of ABZ on non-small cell lung cancer (NSCLC) cells and explore the underlying molecular mechanisms. The expression levels of HIF-1α and VEGF were detected using western blot analysis, and the effect of ABZ on glycolysis was evaluated by measuring the relative activities of hexokinase (HK), pyruvate kinase (PK), and lactate dehydrogenase (LDH) and detecting the production of lactate in A549 and H1299 cells. The results showed that ABZ decreased the expression levels of HIF-1α and VEGF and suppressed glycolysis in under hypoxia, but not normoxic condition. Inhibiting HIF-1α also suppressed glycolysis and VEGF expression. Additionally, ABZ inhibited the volume and weight, decreased the relative activities of HK, PK, and LDH, and reduced the levels of HIF-1α and VEGF of A549 xenografts in mouse models. In conclusion, ABZ inhibited growth of NSCLC cells by suppressing HIF-1α-dependent glycolysis and VEGF expression.
KeywordsAlbendazole HIF-1α Glycolysis VEGF Non-small cell lung cancer
We thank all the members in our department for their help in experiment methods suggestion and data collection.
Compliance with ethical standards
Conflict of interest
All authors declared that no competing interests existed.
- 20.Ahn GO, Seita J, Hong BJ, Kim YE, Bok S, Lee CJ, Kim KS, Lee JC, Leeper NJ, Cooke JP, Kim HJ, Kim IH, Weissman IL, Brown JM (2014) Transcriptional activation of hypoxia-inducible factor-1 (HIF-1) in myeloid cells promotes angiogenesis through VEGF and S100A8. Proc Natl Acad Sci USA 111(7):2698–2703CrossRefPubMedPubMedCentralGoogle Scholar
- 23.Liu JS, Liu J (2013) Effect of Albendazole on proliferation and apoptosis of human colon carcinoma SW480 cells and Bcl-2 expression. Chin J Biol 26(5):685–689Google Scholar
- 30.Giatromanolaki A, Koukourakis MI, Sivridis E, Turley H, Talks K, Pezzella F, Gatter KC, Harris AL (2001) Relation of hypoxia inducible factor 1α and 2α in operable non-small cell lung cancer to angiogenic/molecular profile of tumours and survival[J]. Br J Cancer 85(6):881–890CrossRefPubMedPubMedCentralGoogle Scholar