Abstract：
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).
CONCLUSIONS: 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.
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).
CONCLUSIONS: 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.
摘要：
目的：结直肠癌（CRC）是一种由于遗传变异和表观遗传改变而逐渐发展的肿瘤性疾病。手术切除是CRC的一线治疗。越来越多的证据表明，全静脉麻醉对CRC患者具有有益的作用，因为它降低了肿瘤复发和转移的可能性。丙泊酚是临床上最经常使用的静脉麻醉药之一。然而,目前尚不清楚它是否能减少癌症患者手术后的复发和转移。
方法：体外培养CRC细胞系（HCT116和SW480），细胞培养基中加入不同浓度的丙泊酚。通过CCK-8测定评价异丙酚对CRC细胞系的增殖作用。通过划痕愈合和Transwell实验评价异丙酚对CRC细胞迁移和侵袭的影响。采用Westernblotting和免疫荧光法检测异丙酚对CRC细胞株NF-κB和HIF-1α表达的抑制作用，进一步阐明异丙酚对NF-κB和HIF-1α的调控作用。
结果：与对照组相比，异丙酚明显抑制增殖，迁移,和CRC细胞的侵袭能力（HCT116和SW480）（P<0.0001）。NF-κB和HIF-1α在两种细胞系中的表达水平随着异丙酚浓度的增加而逐渐降低。激活和抑制NF-κB后，HIF-1α的表达发生变化。进一步研究表明丙泊酚抑制LPS激活的NF-κB诱导的HIF-1α表达,与NF-κB抑制剂Bay17083相似(P<0.0001)。
结论：在体外，异丙酚抑制增殖，迁移,和CRC细胞的侵袭（HCT116和SW480）以剂量依赖的方式，可能通过参与NF-κB/HIF-1α信号通路的调控。
方法：体外培养CRC细胞系（HCT116和SW480），细胞培养基中加入不同浓度的丙泊酚。通过CCK-8测定评价异丙酚对CRC细胞系的增殖作用。通过划痕愈合和Transwell实验评价异丙酚对CRC细胞迁移和侵袭的影响。采用Westernblotting和免疫荧光法检测异丙酚对CRC细胞株NF-κB和HIF-1α表达的抑制作用，进一步阐明异丙酚对NF-κB和HIF-1α的调控作用。
结果：与对照组相比，异丙酚明显抑制增殖，迁移,和CRC细胞的侵袭能力（HCT116和SW480）（P<0.0001）。NF-κB和HIF-1α在两种细胞系中的表达水平随着异丙酚浓度的增加而逐渐降低。激活和抑制NF-κB后，HIF-1α的表达发生变化。进一步研究表明丙泊酚抑制LPS激活的NF-κB诱导的HIF-1α表达,与NF-κB抑制剂Bay17083相似(P<0.0001)。
结论：在体外，异丙酚抑制增殖，迁移,和CRC细胞的侵袭（HCT116和SW480）以剂量依赖的方式，可能通过参与NF-κB/HIF-1α信号通路的调控。
