卡里霉素对口腔鳞状细胞癌细胞的体内外抗肿瘤作用。
Anti-tumor effect of carrimycin on oral squamous cell carcinoma cells in vitro and in vivo.
作者信息
Liang Si-Yuan, Zhao Tong-Chao, Zhou Zhi-Hang, Ju Wu-Tong, Liu Ying, Tan Yi-Ran, Zhu Dong-Wang, Zhang Zhi-Yuan, Zhong Lai-Ping
机构信息
Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, No. 639 Zhizaoju Road, Shanghai 200011, China.
Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, No. 639 Zhizaoju Road, Shanghai 200011, China.
出版信息
Transl Oncol. 2021 Jun;14(6):101074. doi: 10.1016/j.tranon.2021.101074. Epub 2021 Mar 18.
PURPOSE
Carrimycin is a newly synthesized macrolide antibiotic with good antibacterial effect. Exploratory experiments found its function in regulating cell physiology, proliferation and immunity, suggesting its potential anti-tumor capacity. The aim of this study is to investigate the anti-tumor effect of carrimycin against human oral squamous cell carcinoma cells in vitro and in vivo.
METHODS
Human oral squamous cell carcinoma cells (HN30/HN6/Cal27/HB96 cell lines) were treated with gradient concentration of carrimycin. Cell proliferation, colony formation and migration ability were analyzed. Cell cycle and apoptosis were assessed by flow cytometry. The effect of carrimycin on OSCC in vivo was investigated in tumor xenograft models. Immunohistochemistry, western blot assay and TUNEL assays of tissue samples from xenografts were performed. The key proteins in PI3K/AKT/mTOR pathway and MAPK pathway were examined by western blot.
RESULTS
As the concentration of carrimycin increased, the proliferation, colony formation and migration ability of OSCC cells were inhibited. After treating with carrimycin, cell cycle was arrested in G0/G1 phase and cell apoptosis was promoted. The tumor growth of xenografts was significantly suppressed. Furthermore, the expression of p-PI3K, p-AKT, p-mTOR, p-S6K, p-4EBP1, p-ERK and p-p38 were down-regulated in vitro and in vivo.
CONCLUSIONS
Carrimycin can inhibit the biological activities of OSCC cells in vitro and in vivo, and regulate the PI3K/AKT/mTOR and MAPK pathways.
目的
卡里霉素是一种新合成的大环内酯类抗生素，具有良好的抗菌效果。探索性实验发现其在调节细胞生理、增殖和免疫方面的作用，提示其具有潜在的抗肿瘤能力。本研究旨在探讨卡里霉素在体外和体内对人口腔鳞状细胞癌细胞的抗肿瘤作用。
方法
用梯度浓度的卡里霉素处理人口腔鳞状细胞癌细胞（HN30/HN6/Cal27/HB96细胞系）。分析细胞增殖、集落形成和迁移能力。通过流式细胞术评估细胞周期和凋亡。在肿瘤异种移植模型中研究卡里霉素对体内口腔鳞状细胞癌的作用。对异种移植组织样本进行免疫组织化学、蛋白质印迹分析和TUNEL检测。通过蛋白质印迹法检测PI3K/AKT/mTOR途径和MAPK途径中的关键蛋白。
结果
随着卡里霉素浓度的增加，口腔鳞状细胞癌细胞的增殖、集落形成和迁移能力受到抑制。用卡里霉素处理后，细胞周期停滞在G0/G1期，细胞凋亡增加。异种移植瘤的生长明显受到抑制。此外，体外和体内p-PI3K、p-AKT、p-mTOR、p-S6K、p-4EBP1、p-ERK和p-p38的表达均下调。
结论
卡里霉素可在体外和体内抑制口腔鳞状细胞癌细胞的生物学活性，并调节PI3K/AKT/mTOR和MAPK途径。
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