Department of Hematology and Oncology, Chang Gung Memorial Hospital at Chiayi, Taiwan.
Int J Radiat Oncol Biol Phys. 2010 Mar 15;76(4):1214-24. doi: 10.1016/j.ijrobp.2009.09.059.
Tumor eradication by chemoradiotherapy for pharyngeal cancer has not been particularly successful. Targeting epithelial growth factor receptor (EGFR) could be a potential treatment strategy providing additional benefits, but only a subset of these tumors gives a clinically significant response to EGFR inhibitors. The aim has been to identify the role of interleukin-6 (IL-6) signaling and its predictive power in the treatment response of pharyngeal cancer.
Human pharyngeal cancer cell lines, including the hypopharyngeal cancer cell line FaDu and its derived cell line FaDu-C225-R, were selected. Changes in tumor growth, response to treatment, and responsible signaling pathway were investigated in vitro. Furthermore, 95 pharyngeal cancer tissue specimens were analyzed by immunohistochemical staining, and correlations were made between levels of IL-6, IL-6 receptor (IL-6R), p-AKT, and p-STAT3 expression and the clinical outcome of patients.
In vitro, either extrinsic IL-6 stimulation of cancer cells or intrinsically activated IL-6 signaling detected in FADu-C225-R cells results in resistance to irradiation and EGFR inhibitor. Blocking IL-6 signaling attenuated aggressive tumor behavior and sensitized the cells to treatments. The responsible mechanisms included decreased p-STAT3, less nuclear translocation of EGFR, and subsequently attenuated epithelial-mesenchymal transition. Regarding clinical data, staining of p-STAT3 and IL-6 was significantly linked with lower response rates to treatments and shorter survival in pharyngeal cancer patients.
IL-6 and p-STAT3 may be significant predictors of pharyngeal carcinoma, and regulating IL-6 signaling can be considered a promising therapeutic approach.
放化疗未能彻底清除咽癌肿瘤。针对表皮生长因子受体（EGFR）可能是一种潜在的治疗策略，可以提供额外的益处，但只有一部分肿瘤对 EGFR 抑制剂有显著的临床反应。本研究旨在确定白细胞介素-6（IL-6）信号及其在咽癌治疗反应中的预测能力的作用。
选择人咽癌细胞系，包括下咽癌细胞系 FaDu 和其衍生的 FaDu-C225-R 细胞系。在体外研究肿瘤生长、治疗反应和相关信号通路的变化。此外，对 95 例咽癌组织标本进行免疫组化染色，并分析 IL-6、IL-6 受体（IL-6R）、p-AKT 和 p-STAT3 表达水平与患者临床结局之间的相关性。
在体外，癌细胞的外源性 IL-6 刺激或在 FaDu-C225-R 细胞中检测到的内在激活的 IL-6 信号均可导致对放疗和 EGFR 抑制剂的耐药性。阻断 IL-6 信号可减弱侵袭性肿瘤行为，并使细胞对治疗敏感。负责的机制包括减少 p-STAT3、EGFR 核转位减少，随后减弱上皮-间充质转化。关于临床数据，p-STAT3 和 IL-6 的染色与咽癌患者治疗反应率降低和生存时间缩短显著相关。
IL-6 和 p-STAT3 可能是咽癌的重要预测因子，调节 IL-6 信号可能被认为是一种有前途的治疗方法。
