Wu Zhichao, Wang Han, Shi Zu-An, Li Yalan
Department of Anesthesiology, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, 637000 Sichuan, China.
Department of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630 Guangdong, China.
J Oncol. 2022 Apr 30;2022:8317466. doi: 10.1155/2022/8317466. eCollection 2022.
Colorectal cancer (CRC) is one of the most frequently diagnosed gastrointestinal malignancies worldwide and has high rates of morbidity and mortality. Propofol has been reported to have certain anticancer properties. However, the role and mechanism of propofol in CRC are not entirely clear. CRC cells were treated with propofol and/or LDH-overexpression plasmids, and a mouse xenograft model of CRC was also established and treated with propofol. Cell viability, migration, and invasion were evaluated by CCK-8, wound healing, and transwell assays; the expression of related proteins was confirmed by western blotting; indexes of the glycolytic pathway were analyzed using specialized kits; tumor growth in mice was measured; pathological tissue structure was assessed by H&E staining; and 8-OHDG expression was determined by an immunochemistry assay. Our results verified that propofol could effectively prevent the malignant behaviors of CRC cells by suppressing cell viability, migration, and invasion and accelerating apoptosis. We also discovered that propofol could attenuate the glycolytic pathway in CRC cells. Moreover, we proved that lactate dehydrogenase (LDH) was required for the inhibitory effects of propofol on the growth of CRC cells, including glycolysis in CRC cells. Furthermore, our results showed that propofol could not only significantly inhibit tumor growth and glycolysis, but also ameliorate the pathological structure of CRC tumors. The current results proved that propofol could attenuate the malignant progression of CRC by preventing LDH activity, suggesting that propofol might be an effective therapeutic agent for CRC.
结直肠癌（CRC）是全球最常被诊断出的胃肠道恶性肿瘤之一，发病率和死亡率都很高。据报道，丙泊酚具有一定的抗癌特性。然而，丙泊酚在结直肠癌中的作用和机制尚不完全清楚。用丙泊酚和/或乳酸脱氢酶（LDH）过表达质粒处理结直肠癌细胞，并建立结直肠癌小鼠异种移植模型并用丙泊酚进行处理。通过CCK-8、伤口愈合和Transwell实验评估细胞活力、迁移和侵袭能力；通过蛋白质免疫印迹法确认相关蛋白的表达；使用专用试剂盒分析糖酵解途径的指标；测量小鼠体内肿瘤的生长情况；通过苏木精-伊红（H&E）染色评估病理组织结构；通过免疫化学分析确定8-羟基脱氧鸟苷（8-OHDG）的表达。我们的结果证实，丙泊酚可通过抑制细胞活力、迁移和侵袭以及加速细胞凋亡，有效预防结直肠癌细胞的恶性行为。我们还发现丙泊酚可减弱结直肠癌细胞中的糖酵解途径。此外，我们证明丙泊酚对结直肠癌细胞生长的抑制作用，包括对结直肠癌细胞糖酵解的抑制作用，需要乳酸脱氢酶（LDH）。此外，我们的结果表明，丙泊酚不仅可以显著抑制肿瘤生长和糖酵解，还可以改善结直肠癌肿瘤的病理结构。目前的结果证明，丙泊酚可通过抑制LDH活性减弱结直肠癌的恶性进展，这表明丙泊酚可能是一种有效的结直肠癌治疗药物。
