Department of Obstetrics and Gynecology, The First Affiliated Hospital of the University of Science and Technology of China, Anhui Provincial Hospital, Hefei, Anhui 230001, P.R. China.
Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230601, P.R. China.
Oncol Rep. 2021 Feb;45(2):606-618. doi: 10.3892/or.2020.7889. Epub 2020 Dec 8.
Claudin 1 is a member of the claudin protein family that serves an important role in tight junctions. Increased or decreased expression levels of claudin 1 are found in several diseases, including breast cancer and viral infections. However, the function of claudin 1 in cervical cancer remains controversial. The aim of the present study was to investigate the biological functions of claudin 1 in different human cervical cancer cell lines. First, SiHa and ME‑180 cells with stable claudin 1 overexpression or knockdown were established using lentiviral transduction, and the mRNA and protein levels were measured via reverse transcription‑quantitative PCR and western blot analysis. Subsequently, cell proliferation, colony formation and migration experiments were performed in vitro using standard protocols, demonstrating that claudin 1 was able to inhibit cell proliferation and migration in both SiHa and ME‑180 cells. Furthermore, cell cycle and apoptosis were detected via flow cytometry and western blotting, and the results revealed that claudin 1 inhibited cell cycle progression and promoted apoptosis. To further verify whether claudin 1 was involved in tumor growth in vivo, xenograft tumors were established in athymic mice via injecting SiHa cells overexpressing claudin 1, which was found to decrease tumor growth in vivo. Furthermore, the association between claudin 1 expression and prognosis was analyzed in different types of cancer in The Cancer Genome Atlas. Overall, the findings of the present study revealed that claudin 1 may serve an antitumor role in cervical squamous cell carcinoma and may be of value as a potential therapeutic target.
紧密连接相关蛋白家族成员 Claudin-1 在细胞间紧密连接中发挥着重要作用。Claudin-1 的表达水平在包括乳腺癌和病毒感染在内的多种疾病中升高或降低。然而,Claudin-1 在宫颈癌中的作用仍存在争议。本研究旨在探讨 Claudin-1 在不同人宫颈癌细胞系中的生物学功能。首先,通过慢病毒转导构建 Claudin-1 过表达或敲低稳定株的 SiHa 和 ME-180 细胞,并通过逆转录-定量 PCR 和 Western blot 分析测量 mRNA 和蛋白水平。随后,根据标准方案进行体外细胞增殖、集落形成和迁移实验,结果表明 Claudin-1 能够抑制 SiHa 和 ME-180 细胞的增殖和迁移。此外,通过流式细胞术和 Western blot 检测细胞周期和凋亡,结果表明 Claudin-1 抑制细胞周期进程并促进凋亡。为了进一步验证 Claudin-1 是否参与体内肿瘤生长,通过注射过表达 Claudin-1 的 SiHa 细胞在裸鼠中建立异种移植瘤,发现 Claudin-1 能够在体内抑制肿瘤生长。此外,还分析了癌症基因组图谱中不同类型癌症中 Claudin-1 表达与预后之间的关系。综上所述,本研究结果表明 Claudin-1 可能在宫颈鳞状细胞癌中发挥抗肿瘤作用,并且可能作为一种有价值的潜在治疗靶点。