Title:The Inhibitory Effects of Propofol on Colorectal Cancer Progression through the
NF-κB/HIF-1α Signaling Pathway
Volume: 24
Issue: 11
Author(s): Liuxu Yao, Wen Zhai, Zongming Jiang, Rui He, Weiying Xie, Yuhong Li*Yiyang Hu*
Affiliation:
- Department of Anesthesiology, Shulan (Hangzhou) Hospital, Shulan International Medical College, Zhejiang Shuren College, Hangzhou, Zhejiang, China
- Center for Rehabilitation Medicine, Department of Anesthesiology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
Keywords:
Colorectal cancer, propofol, nuclear factor-κB, hypoxia-inducible factor-1α, genetic variations, CCK-8 assay.
Abstract:
Background and Objective: 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.
Methods: 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.
Results: 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).
Conclusion: 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.
