Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
J Dig Dis. 2017 Sep;18(9):511-520. doi: 10.1111/1751-2980.12496.
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.
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.
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.
The IL-1α/hypoxia axis may be a valuable target for diagnosis and treatment of GC.
肿瘤微环境构成了促进癌症转移和耐药的独特生态位。该微环境的两个显著特征是缺氧和炎症。白细胞介素-1α（IL-1α）是一种重要的炎症因子，在多种癌症中经常上调。本研究旨在研究 IL-1α在胃癌（GC）中的表达，并探讨 IL-1α与缺氧之间的关系。
采用逆转录聚合酶链反应（RT-PCR）方法检测不同 GC 细胞系在常氧或缺氧条件下 IL-1α的表达。分析 IL-1α表达与 GC 肿瘤分期和淋巴结转移以及患者生存的关系。还评估了在常氧或缺氧条件下敲低 IL-1α对细胞增殖、迁移和对顺铂敏感性的影响。此外，通过过表达外源性 HIF-1α或通过 shHIF-1α 转染下调 KATO-III 细胞中的缺氧诱导因子-1α（HIF-1α）表达，随后评估其对 IL-1α表达的影响。
在 GC 中，IL-1α在缺氧时上调，与肿瘤分期、淋巴结转移和对顺铂的耐药性呈正相关。IL-1α受 HIF1α调节，HIF1α 表达的改变改变了 IL-1α的促肿瘤作用。
IL-1α/缺氧轴可能是 GC 诊断和治疗的有价值的靶点。
