Department of Otorhinolaryngology Head and Neck Surgery, the Yijishan Hospital of Wannan Medical College, Wuhu, 241001, China.
Curr Med Sci. 2022 Aug;42(4):832-840. doi: 10.1007/s11596-022-2615-3. Epub 2022 Jul 21.
Follistatin (FST) inhibits the action of activin by interfering with the binding of activin to its receptor. Although the prognostic value of FST in various cancers has been investigated previously, studies rarely focused on hypopharyngeal carcinoma (HPC). In our study, the effect of FST expression on HPC tissues and cell lines was investigated.
A total of 60 patients with HPC were recruited for this study. Levels of FST mRNA and protein were measured by quantitative polymerase chain reaction (PCR) and immunohistochemistry in HPC tissue samples and by qPCR in the HPC FaDu cells, as well as immortal nasopharyngeal epithelial cell line NP-69 cells. After silencing the FST expression in FaDu cells using lentivirus-mediated siRNA that was specific for FST mRNA, cell proliferation was determined by a Celigo assay. Tumor growth was monitored in nude mice and viability was determined by a methylthiazoletetrazolium assay. The ratio of cell cycle arrest and apoptosis was evaluated by flow cytometry. The colony formation ability was performed using Giemsa staining. In addition, wound healing and Transwell migration and invasion assays were performed for the analysis of cell motility.
FST expression was significantly higher in human HPC tissue and FaDu cells than in normal tissue and NP-69 cells. A higher expression of FST in HPC samples was positively correlated with advanced tumors. Moreover, FST knockdown by shRNA significantly decreased cell growth, colony formation, migration and invasion. Furthermore, FST silencing increased the cell apoptosis percentage, and arrested cell cycle in the S phase in FaDu cells. In addition, FST silencing suppressed tumor growth in vivo.
Our results indicated that the FST gene was associated with HPC progression and may serve as a potential therapeutic target for the treatment of HPC.
卵泡抑素（Follistatin，FST）通过干扰激活素与其受体的结合来抑制激活素的作用。尽管先前已经研究了 FST 在各种癌症中的预后价值，但研究很少关注下咽癌（Hypopharyngeal Carcinoma，HPC）。在本研究中，我们研究了 FST 表达对上皮性 HPC 组织和细胞系的影响。
本研究共纳入 60 例 HPC 患者。通过定量聚合酶链反应（PCR）和免疫组织化学检测 HPC 组织样本中 FST mRNA 和蛋白的水平，通过 qPCR 检测 HPC FaDu 细胞和永生化鼻咽上皮细胞系 NP-69 细胞中 FST 的水平。使用特异性针对 FST mRNA 的慢病毒介导的 siRNA 沉默 FaDu 细胞中的 FST 表达后，通过 Celigo 法测定细胞增殖。裸鼠监测肿瘤生长，甲基噻唑蓝比色法测定细胞活力。通过流式细胞术评估细胞周期阻滞和凋亡的比例。通过吉姆萨染色进行集落形成能力测定。此外，还进行了划痕愈合和 Transwell 迁移和侵袭实验，以分析细胞运动性。
FST 在人 HPC 组织和 FaDu 细胞中的表达明显高于正常组织和 NP-69 细胞。HPC 样本中 FST 的高表达与晚期肿瘤呈正相关。此外，shRNA 下调 FST 表达显著降低了 FaDu 细胞的生长、集落形成、迁移和侵袭。此外，FST 沉默增加了 FaDu 细胞的凋亡比例，并使细胞周期在 S 期停滞。此外，FST 沉默抑制了体内肿瘤的生长。
我们的研究结果表明，FST 基因与 HPC 的进展有关，可能作为治疗 HPC 的潜在治疗靶点。
