Division of Vascular and Interventional Radiology, Department of General Surgery, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, Guangdong, People's Republic of China.
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
Clin Transl Oncol. 2021 Sep;23(9):1847-1856. doi: 10.1007/s12094-021-02594-w. Epub 2021 Apr 5.
Hepatocellular carcinoma is one of the most common malignancies and leading cancer-associated deaths worldwide. Ozone has been proposed as a promising therapeutic agent in the treatment of various disorders.
The purpose of this paper is to assess the potential anticancer effects of the ozone on liver cancer cells.
The liver cancer cell line of bel7402 and SMMC7721 was used in this study. Proliferation was evaluated using the CCK-8 and the colony formation assay. Wond healing assay and transwell assay without Matrigel were used to evaluate their migration ability. Flow cytometry was used for cell cycle analysis and reactive oxygen species (ROS) determination. Glutathione detection kit was used for measurement of glutathione level. Protein expression was estimated by western blot analysis.
Ozone treatment inhibited liver cancer cell proliferation, colony formation. Ozone induced G2/M phase cell cycle arrest, which could be elucidated by the change of protein levels of p53, p21, Cyclin D1, cyclin B1, cdc2, and CDK4. We also found that ozone treatment inhibited migration ability by inhibiting EMT-relating protein. Ozone also induced ROS accumulation and decreased glutathione level decreased, which contributed to the inactivation of the PI3K/AKT/NF-κB pathway. Finally, we found that pre-treatment of liver cancer cells with N-acetylcysteine resisted ozone-induced effects.
Ozone restrains the proliferation and migration potential and EMT process of liver cancer cells via ROS accumulation and PI3K/AKT/NF-κB suppression.
肝细胞癌是全球最常见的恶性肿瘤之一，也是导致癌症相关死亡的主要原因。臭氧已被提议作为治疗各种疾病的一种有前途的治疗剂。
本文旨在评估臭氧对肝癌细胞的潜在抗癌作用。
本研究采用肝癌细胞系 bel7402 和 SMMC7721。用 CCK-8 和集落形成实验评估增殖。无 Matrigel 的划痕愈合实验和 Transwell 实验用于评估其迁移能力。流式细胞术用于细胞周期分析和活性氧（ROS）测定。谷胱甘肽检测试剂盒用于测量谷胱甘肽水平。通过 Western blot 分析估计蛋白质表达。
臭氧处理抑制肝癌细胞增殖、集落形成。臭氧诱导 G2/M 期细胞周期停滞，这可以通过 p53、p21、Cyclin D1、cyclin B1、cdc2 和 CDK4 蛋白水平的变化来阐明。我们还发现臭氧处理通过抑制 EMT 相关蛋白来抑制迁移能力。臭氧还诱导 ROS 积累，降低谷胱甘肽水平，从而导致 PI3K/AKT/NF-κB 通路失活。最后，我们发现肝癌细胞用 N-乙酰半胱氨酸预处理可抵抗臭氧诱导的作用。
臭氧通过 ROS 积累和 PI3K/AKT/NF-κB 抑制抑制肝癌细胞的增殖和迁移潜力以及 EMT 过程。
