中国口腔颌面外科杂志

中国口腔颌面外科杂志 ›› 2022, Vol. 20 ›› Issue (3): 219-224.doi: 10.19438/j.cjoms.2022.03.002

• 论著 • 上一篇    下一篇

EGFR靶向药物对口腔癌疼痛缓解作用的机制探讨

魏东亮, 李智, 鞠侯雨, 吴云腾, 郭伟, 任国欣   

  1. 上海交通大学医学院附属第九人民医院 口腔颌面-头颈肿瘤科,上海交通大学口腔医学院, 国家口腔医学中心,国家口腔疾病临床医学研究中心,上海市口腔医学重点实验室,上海 200011
  • 收稿日期:2021-04-12 修回日期:2022-02-16 出版日期:2022-05-20 发布日期:2022-05-20
  • 通讯作者: 任国欣,E-mail：renguoxincn@sina.com
  • 作者简介:魏东亮（1995-）,男,硕士研究生,E-mail：weidongliang@sjtu.edu.cn

Mechanism of EGFR-targeted drugs for pain relief in oral cancer

WEI Dong-liang, LI Zhi, JU Hou-yu, WU Yun-teng, GUO Wei, REN Guo-xin   

  1. Department of Oromaxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology. Shanghai 200011, China
  • Received:2021-04-12 Revised:2022-02-16 Online:2022-05-20 Published:2022-05-20

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摘要： 目的: 探讨针对EGFR靶点的药物（厄洛替尼、尼妥珠单抗）是否影响实验动物的痛阈并初步分析其机制。方法: 正常小鼠分为2组（生理盐水,n=6;厄洛替尼,n=6）,给药后1 h采用Von Frey纤维丝法、热板法、5%（中性）甲醛致痛实验比较2组动物的痛阈差异。选取正常裸鼠分为3组（Sham组+NS组,n=10;足底成瘤+NS组,n=10;足底成瘤+尼妥珠单抗组,n=10）,分别检测造模前1 d,造模后1、5、7、10、14 d小鼠机械痛阈、热痛阈。14 d后解剖小鼠足爪,组织匀浆后以ELISA法检测IL-1β、IL-6等细胞因子浓度。采用Graphpad Prism软件包处理数据。结果: 注射厄洛替尼后,小鼠机械痛阈、热痛阈无明显变化。注射5%（中性）甲醛后,小鼠前相（0~10 min,P<0.01）、后相（10~60 min,P<0.01）舔咬时间显著减少。裸鼠足底成瘤后可诱发小鼠热痛敏、机械痛敏,尼妥珠单抗可提高成瘤小鼠的热痛阈（P<0.05）及机械痛阈值（P<0.05）。ELISA分析显示,尼妥珠单抗治疗组小鼠足爪组织中IL-1β、IL-6浓度较PBS治疗组显著降低（P<0.05）。结论: 厄洛替尼可降低5%甲醛引发的小鼠疼痛;尼妥珠单抗可减少足底成瘤引发的机械痛敏和热痛敏,其机制可能与局部组织中炎性细胞因子降低有关。EGFR靶向药物或可成为晚期癌痛患者良好的镇痛药物之一。

关键词: 尼妥珠单抗, 厄洛替尼, 疼痛, 口腔鳞癌

Abstract: PURPOSE: The purpose of this study was to investigate whether drugs targeting EGFR (erlotinib, Nimotuzumab) could affect the pain threshold of experimental animals and to preliminarily explore the mechanism. METHODS: Naive mice were divided into two groups(physiological saline, n=6; erlotinib, n=6), the difference of pain threshold between the two groups was compared by Von Frey fiber test, hot plate test and 5% formalin test 1 h after administration. Nude mice were selected and divided into 3 groups (Sham + NS group, n=10; Plantar neoplasia + NS group, n=10; Plantar neoplasia + Nimotuzumab group, n=10). The mechanical pain threshold and thermal pain threshold of the mice were detected 1d before modeling and 1, 5, 7, 10 and 14 d after modeling. The mouse feet were dissected 14 days later, and the concentrations of IL-1β and IL-6 were detected by ELISA after tissue homogenization. The data were processed by Graphpad Prism statistical software. RESULTS: After erlotinib injection, the mechanical pain threshold and thermal pain threshold of mice had no obvious changes. After injection of 5% formalin in mice, the duration of licking in the anterior phase (0-10 min, P<0.01) and posterior phase (10-60 min, P<0.01) decreased significantly. Heat and mechanical pain sensitivity could be induced after plantar tumor formation in nude mice. Nimotuzumab slowed down tumor growth rate and increased thermal pain threshold (P<0.05) and mechanical pain threshold (P<0.05) in plantar tumorigenic mice. ELISA showed that the concentration of IL-1β (P<0.05) and IL-6 (P<0.05) in the plantar tissue of mice in the Nimotuzumab treatment group was significantly lower than that of the PBS treatment group. CONCLUSIONS: Erlotinib can alleviate pain induced by formalin in mice. Nimotuzumab can reduce mechanical and thermal pain sensitivity induced by plantar tumor formation, and the mechanism may be related to the decrease of inflammatory cytokines in local tissues. EGFR-targeted drugs may be one of the good analgesics for patients with advanced cancer pain.

Key words: Nimotuzumab, Erlotinib, Pain, Oral squamous cell carcinoma

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