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

OBJECTIVE: The microenvironment of tumors constitutes a unique niche that promotes cancer metastasis and resistance. Two remarkable characteristics of this microenvironment are hypoxia and inflammation. Interleukin-1α (IL-1α), an important inflammatory factor, is frequently upregulated in a variety of cancers. This study aimed to investigate the expression of IL-1α in gastric cancer (GC) and explore the relationship between IL-1α and hypoxia.

METHODS: Reverse-transcription polymerase chain reaction was performed to characterize IL-1α expression in different GC cell lines under normoxia or hypoxia. IL-1α expression was characterized in relation to tumor stage and lymph node metastasis of GC and the survival of patients. The effect of IL-1α knockdown under normoxia or hypoxia on cell proliferation, migration and sensitivity to cisplatin was also evaluated. Additionally, hypoxia-inducible factor-1α (HIF-1α) expression in KATO-III cells was either upregulated by ectopic HIF-1α expression or downregulated through shHIF-1α transfection, the effects of which on IL-1α expression was subsequently evaluated.

RESULTS: There was a positive correlation between IL-1α, which was upregulated during hypoxia, and tumor stage, lymph node metastasis and resistance to cisplatin in GC. IL-1α was regulated by HIF1α, and a change in HIF1α expression altered the tumor-promoting effect of IL-1α.

CONCLUSION: The IL-1α/hypoxia axis may be a valuable target for diagnosis and treatment of GC.