The Inhibitory Effects of Propofol on Colorectal Cancer Progression through the NF-κB/HIF-1α Signaling Pathway

• Published in: Anti-cancer agents in medicinal chemistry
• Main Authors: Yao, Liuxu, Zhai, Wen, Jiang, Zongming, He, Rui, Xie, Weiying, Li, Yuhong, Hu, Yiyang
• Format: Journal Article
• Language: English
• Published: Netherlands 01.01.2024
• Subjects: nuclear factor-κB; hypoxia-inducible factor-1β; propofol; Colorectal cancer
• ISSN: 1875-5992
• DOI: 10.2174/0118715206283884240326170501

Colorectal cancer (CRC) is a neoplastic disease that gradually develops due to genetic variations and epigenetic changes. Surgical excision is the first-line treatment for CRC. Accumulating evidence has shown that total intravenous anesthesia has beneficial effects for CRC patients as it decreases the probability of tumor recurrence and metastasis. Propofol is one of the most frequently used intravenous anesthetics in clinical practice. However, it remains unknown whether it can reduce recurrence and metastasis after surgery in cancer patients. CRC cell lines (HCT116 and SW480) were cultured in vitro, and different concentrations of propofol were added to the cell culture medium. The proliferation effect of propofol on CRC cell lines was evaluated by CCK-8 assay. The effect of propofol on the migration and invasion of CRC cells was evaluated by scratch healing and Transwell experiments. The inhibitory effects of propofol on NF-κB and HIF-1α expressions in CRC cell lines were determined by Western blotting and immunofluorescence assays to further clarify the regulatory effects of propofol on NF-κB and HIF-1α. Compared to the control, propofol significantly inhibited the proliferation, migration, and invasion abilities of CRC cells (HCT116 and SW480) (P < 0.0001). The expression levels of NF-κB and HIF-1α gradually decreased with increasing propofol concentration in both cell lines. After activation and inhibition of NF-κB, the expression of HIF-1α changed. Further studies showed that propofol inhibited LPS-activated NF-κB-induced expression of HIF-1α, similar to the NF-κB inhibitor Bay17083 (P < 0.0001). In vitro, propofol inhibited the proliferation, migration, and invasion of CRC cells (HCT116 and SW480) in a dose-dependent manner, possibly by participating in the regulation of the NF-κB/HIF-1α signaling pathway.