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维生素C促进口腔鳞状细胞癌的细胞凋亡和细胞周期停滞。

Vitamin C Promotes Apoptosis and Cell Cycle Arrest in Oral Squamous Cell Carcinoma.

作者信息

Zhou Jianjun, Chen Chen, Chen Xiaoqing, Fei Yifan, Jiang Lei, Wang Guodong

机构信息

Department of Stomatology, Changzheng Hospital, Second Military Medical University, Shanghai, China.

出版信息

Front Oncol. 2020 Jun 10;10:976. doi: 10.3389/fonc.2020.00976. eCollection 2020.

Abstract

Oral squamous cell carcinoma (OSCC) is currently ranked as the eighth most prevalent type of cancer. Despite recent advances in cancer research, the 8-year survival rate for oral squamous cell carcinoma remains only 50-60%. Therefore, markers for early detection, identification of efficient chemotherapeutic agents, and post-therapeutic monitoring are the immediate needs. With this background, this study was designed to investigate the anticancer effects of vitamin C (VC) in oral squamous cell carcinoma. Our results showed that VC had an anticancer effect on the oral squamous cell lines used in this study. VC also showed an inhibitory effect on xenograft tumors in nude mice and had a synergistic effect with cisplatin to induce cell apoptosis. Mechanistically, VC caused a significant increase in the levels of reactive oxygen species (ROS), which led to induced genotoxic (DNA damage) and metabolic (ATP depletion) stresses, inhibited Bcl-2 expression, and promoted Bax expression and caspase-3 cleavage. VC also caused cell cycle arrest at the G0/G1 phase in OSCC cells, which is related to the activation of tumor suppressor p53 and cyclin-dependent kinase inhibitor p21. In conclusion, VC bears considerable therapeutic potential for the treatment of oral squamous cell carcinoma.

摘要

口腔鳞状细胞癌(OSCC)目前是第八大最常见的癌症类型。尽管癌症研究最近取得了进展,但口腔鳞状细胞癌的8年生存率仍仅为50%-60%。因此,早期检测标志物、高效化疗药物的鉴定以及治疗后监测是当务之急。在此背景下,本研究旨在探讨维生素C(VC)对口腔鳞状细胞癌的抗癌作用。我们的结果表明,VC对本研究中使用的口腔鳞状细胞系具有抗癌作用。VC对裸鼠体内的异种移植肿瘤也有抑制作用,并且与顺铂具有协同作用以诱导细胞凋亡。从机制上讲,VC导致活性氧(ROS)水平显著升高,这导致诱导遗传毒性(DNA损伤)和代谢(ATP耗竭)应激,抑制Bcl-2表达,并促进Bax表达和caspase-3裂解。VC还导致OSCC细胞在G0/G1期发生细胞周期阻滞,这与肿瘤抑制因子p53和细胞周期蛋白依赖性激酶抑制剂p21的激活有关。总之,VC在治疗口腔鳞状细胞癌方面具有相当大的治疗潜力。

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