Hypoxia/IL-1α axis promotes gastric cancer progression and drug resistance

OBJECTIVEThe microenvironment of tumors constitutes a unique niche that promotes cancer metastasis and resistance. Two remarkable characteristics of this microenvironment are hypoxia and inflammation. Interleukin-1 (IL-1), an important inflammatory factor, is frequently upregulated in a variety of cancers. This study aimed to investigate the expression of IL-1 in gastric cancer (GC) and explore the relationship between IL-1 and hypoxia. METHODSReverse-transcription polymerase chain reaction was performed to characterize IL-1 expression in different GC cell lines under normoxia or hypoxia. IL-1 expression was characterized in relation to tumor stage and lymph node metastasis of GC and the survival of patients. The effect of IL-1 knockdown under normoxia or hypoxia on cell proliferation, migration and sensitivity to cisplatin was also evaluated. Additionally, hypoxia-inducible factor-1 (HIF-1) expression in KATO-III cells was either upregulated by ectopic HIF-1 expression or downregulated through shHIF-1 transfection, the effects of which on IL-1 expression was subsequently evaluated. RESULTS There was a positive correlation between IL-1, which was upregulated during hypoxia, and tumor stage, lymph node metastasis and resistance to cisplatin in GC. IL-1 was regulated by HIF1, and a change in HIF1 expression altered the tumor-promoting effect of IL-1. CONCLUSIONThe IL-1/hypoxia axis may be a valuable target for diagnosis and treatment of GC.