Interleukin-6 promotes tumor progression in colitis-associated colorectal cancer through HIF-1α regulation

Abstract

Abstract. Interleukin-6 (IL-6) is a well-known etiological factor of colitis-associated colorectal cancer (CAC) and has a significant role in CAC progression. In addition, hypoxia-inducible factor 1α (HIF-1α) serves a primary role in the progression of CAC. However, the association between IL-6 and HIF-1α during the progression of CAC remains unclear. To investigate this association, the present study induced CAC in a mouse model using azoxymethane and dextran sulfate sodium. In addition, an anti-IL-6 receptor antibody was used to inhibit IL-6. In this model, anti-IL-6 receptor antibody treatment significantly inhibited the development of CAC and the expression of HIF-1α, in colorectal adenomas and adenocarcinomas. In patients with CAC, the HIF-1α gene was demonstrated to be overexpressed in tumor tissue compared with adjacent non-malignant tissue. Furthermore, HIF-1α mRNA expression was positively correlated with serum IL-6 concentration. The results of the present study suggest that IL-6 promotes CAC progression, in the early stage of the disease, through HIF-1α regulation.

Preventive effect of pomegranate juice against chemically induced bladder cancer: An experimental study

“…The administration of BBN was related with significant increase in expression of IL-6, TNF-α, HIF-1 and TP53 genes in bladder tissues among the cancer-induced group. IL-6 and TNF-α are pro-inflammatory cytokines that secreted by many cells and play a significant role in carcinogenesis ( Han et al., 2016 ). Both stimulate the conversion of non-cancerous cells into cancerous cells ( Landskron et al., 2014 ).…”

Albumin nano-encapsulation of caffeic acid phenethyl ester and piceatannol potentiated its ability to modulate HIF and NF-kB pathways and improves therapeutic outcome in experimental colitis

“…Several previous findings indicate inflammation results in overstimulation of transcription protein such as p65 and HIF-1α in ulcerative colitis and colorectal cancer which results in damage of epithelial layer of colon [ 57 , 58 ]. Overactivation of nuclear factor p65 and HIF-1α has also been reported in UC patients [ 59 , 60 ].…”

Glycolytic Response to Inflammation Over Time: Role of Myeloid HIF-1alpha

“…In particular, IL-6 an important mediator during the acute response to sepsis that positively correlates with mortality and severity scores in septic patients ( Srisangthong et al, 2013 ), was significantly suppressed in HIF-1DF/LysM mice. Little is known about the correlation between HIF-1α and IL-6 in sepsis, however, in colitis-associated colorectal cancer serum concentrations of IL-6 positively correlated with HIF-1α mRNA levels in the tumor tissue ( Han et al, 2016 ). Consistent with these findings our results suggest that myeloid HIF-1 plays a vital role in regulating IL-6 in sepsis.…”