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

Aim Tumor microenvironment constitutes a unique niche that promotes cancer metastasis and resistance. Two remarkable characteristics of this microenvironment are hypoxia and inflammation. Interleukin-1 alpha (IL1A), an important inflammatory factor, is frequently upregulated in a variety of cancers. Herein, we set force to characterize IL1A expression in gastric cancer and explore the relationship between IL1A and hypoxia. Methods Reverse-transcriptase PCR (RT-PCR) was performed to characterize IL1A expression in different gastric cancer cell lines under normonia or hypoxia. IL1A expression was characterized in correlation to grades, lymph node metastasis, and survival data of gastric cancer patients. The effect of IL1A knockdown, under nomoxia or hypoxia, on cell proliferation, migration, and sensitivity to Cisplatin (CDDP) was also evaluated. Further, HIF-1α expression in KATOIII cells was either upregulated by ectopic HIF-1α expression or downregulated through shHIF-1α transfection, the effects of which on IL1A expression was subsequently evaluated. Results IL1A, which is upregulated during hypoxia, demonstrated positive correlation with the cancer grades, lymph node metastasis, and resistance to CDDP in gastric cancer. IL1A was regulated by HIF1α, and change in HIF1α expression altered the tumor-promoting effect of IL1A. Conclusions The IL1A/hypoxia axis may be a valuable target for diagnosis and therapy of gastric cancer. Copyright © 2017 John Wiley & Sons, Ltd.