Tan Xi, Luo Qiulan, Zhou Shiqing, Huang Wei, Feng Xiaocong, Chen Wenyong, Yang Chaojie, Li Yunying
Otorhinolaryngology Department, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China.
Otorhinolaryngology Department, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, China.
Evid Based Complement Alternat Med. 2020 Apr 22;2020:2803496. doi: 10.1155/2020/2803496. eCollection 2020.
Erchen plus Huiyanzhuyu decoction (EHD), a Chinese herbal medicine (CHM) formula that consists of Erchen decoction and Huiyanzhuyu decoction, has achieved satisfactory results in the clinic. The main function of EHD is to remove phlegm and blood stasis, and EHD is suitable for phlegm-coagulation-blood-stasis (PCBS) syndrome in laryngeal cancer (LC). In this study, a xenograft mouse model of LC with PCBS syndrome was constructed by feeding a high-fat diet, swimming in ice water, and subcutaneously injecting epinephrine hydrochloride for 2 weeks. Based on the successful Chinese medicine syndrome model, Hep2-luciferase-GFP cells were injected subcutaneously under the armpit of the right upper limb in mice to form tumours. A mouse model of LC with PCBS syndrome was established via heterotopic transplantation. Then, the mice received intragastric administration of different concentrations of EHD daily, and cisplatin (DDP) was intraperitoneally injected every week for 21 days. Tumour fluorescence in mice was measured with a living animal imager on days 7, 14, 21, and 28 during treatment. The results of this experiment confirmed that a mouse model of Chinese medicine syndrome was successfully constructed. Moreover, EHD slowed the growth of xenograft tumours in nude mice; decreased the expression levels of STAT3, p-STAT3, and cyclin D1; and upregulated the expression level of P27. In brief, EHD inhibited laryngeal tumour growth in a xenograft mouse model of PCBS syndrome and regulated the STAT3/cyclin D1 signalling pathway. This study was the first to construct a Chinese medicine xenograft mouse model of LC with PCBS syndrome; in addition, this study clarified that EHD regulated the STAT3/cyclin D1 signalling pathway to inhibit the growth of LC and that EHD may be a promising novel therapeutic compound for the treatment of patients with LC.
二陈加化瘀逐瘀汤(EHD)是一种由二陈汤和化瘀逐瘀汤组成的中药配方,在临床上取得了满意的效果。EHD的主要功能是祛痰化瘀,适用于喉癌(LC)中的痰凝血瘀(PCBS)证型。在本研究中,通过高脂饮食、在冰水中游泳以及皮下注射盐酸肾上腺素2周,构建了具有PCBS证型的LC异种移植小鼠模型。在成功建立中医证型模型的基础上,将Hep2-荧光素酶-GFP细胞皮下注射到小鼠右上肢腋窝下以形成肿瘤。通过异位移植建立了具有PCBS证型的LC小鼠模型。然后,小鼠每天接受不同浓度EHD的灌胃给药,每周腹腔注射顺铂(DDP),共21天。在治疗的第7、14、21和28天,用活体动物成像仪测量小鼠的肿瘤荧光。本实验结果证实成功构建了中医证型小鼠模型。此外,EHD减缓了裸鼠异种移植肿瘤的生长;降低了STAT3、p-STAT3和细胞周期蛋白D1的表达水平;并上调了P27的表达水平。简而言之,EHD在PCBS证型的异种移植小鼠模型中抑制了喉肿瘤的生长,并调节了STAT3/细胞周期蛋白D1信号通路。本研究首次构建了具有PCBS证型的LC中药异种移植小鼠模型;此外,本研究阐明了EHD通过调节STAT3/细胞周期蛋白D1信号通路抑制LC的生长,并且EHD可能是一种有前途的新型治疗化合物,用于治疗LC患者。