葉酸營養調節人類結腸癌細胞發炎相關Nuclear factor-κB與侵犯相關Hedgehog訊息傳遞路徑

Folate Status Modulates Inflammatory-associated Nuclear Factor-κB and Invasion-Related Hedgehog Signaling Pathway in Human Colorectal Carcinoma Cells

許舒涵(Shu-Han Hsu) ； 許瑞芬(Rwei-Fen Syu-Huang)

《臺灣營養學會雜誌》 38卷2期 (2013/06) Pp. 29-39

https://doi.org/10.6691/NSJ.201306_38(2).0001

摘要

The chronic inflammatory response and folate malnutrition may increase the risk of developing colorectal cancer. Our previous study showed that folate deprivation modulated the proinflammatory factor of nuclear factor (NF)-κB and Hedgehog (Hh) signaling molecules that were related with colorectal cancer cell invasion. The regulatory mechanism is not clear. The aims of this study were to investigate how the nutritional folate status might modulate NF-κB and the Hh signaling pathway in a human colorectal carcinoma cell line (HCT116). The data revealed that lipopolysaccharide (LPS) treatment significantly promoted IκBα protein degradation of folate-deficient HCT116 cells (p ＜ 0.05). When HCT116 cells were treated with interleukin (IL)-1β for 30 min, IL-1β expression of phospho-Akt, phospho-IκBα, and Gli respectively increased by 1.5-, 4.3-, and 1.3-fold, and total IκBα decreased by 70% (p ＜ 0.0001). Folate supplementation reduced IL-1β-induced protein levels of phospho-Akt by 33% and Gli by 14%, and increased total IκBα by 1.3-fold and tumor necrosis factor (TNF)-α secretion (p ＜ 0.05). Taken together, a folate deficiency or folate supplementation may modulate NF-κB signaling activation to regulate TNF-α secretion through PI3K/Akt and Hh signaling.

關鍵字

結腸癌 ； 葉酸缺乏 ； 葉酸補充 ； NF-κB訊息傳遞 ； Hedgehog訊息傳遞

並列摘要

The chronic inflammatory response and folate malnutrition may increase the risk of developing colorectal cancer. Our previous study showed that folate deprivation modulated the proinflammatory factor of nuclear factor (NF)-κB and Hedgehog (Hh) signaling molecules that were related with colorectal cancer cell invasion. The regulatory mechanism is not clear. The aims of this study were to investigate how the nutritional folate status might modulate NF-κB and the Hh signaling pathway in a human colorectal carcinoma cell line (HCT116). The data revealed that lipopolysaccharide (LPS) treatment significantly promoted IκBα protein degradation of folate-deficient HCT116 cells (p ＜ 0.05). When HCT116 cells were treated with interleukin (IL)-1β for 30 min, IL-1β expression of phospho-Akt, phospho-IκBα, and Gli respectively increased by 1.5-, 4.3-, and 1.3-fold, and total IκBα decreased by 70% (p ＜ 0.0001). Folate supplementation reduced IL-1β-induced protein levels of phospho-Akt by 33% and Gli by 14%, and increased total IκBα by 1.3-fold and tumor necrosis factor (TNF)-α secretion (p ＜ 0.05). Taken together, a folate deficiency or folate supplementation may modulate NF-κB signaling activation to regulate TNF-α secretion through PI3K/Akt and Hh signaling.

並列關鍵字

colorectal cancer ； folate deficiency ； folate supplement ； NF-κB signaling ； Hedgehog signaling