Erchen Plus Huiyanzhuyu Decoction Inhibits the Growth of Laryngeal Carcinoma in a Mouse Model of Phlegm-Coagulation-Blood-Stasis Syndrome via the STAT3/Cyclin D1 Pathway.

Xi Tan,Wei Huang,Chaojie Yang,Wenyong Chen,Shiqing Zhou,Xiaocong Feng,Qiulan Luo,Yunying Li

doi:10.1155/2020/2803496

Abstract

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.

Highlights

Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumour of head and neck cancer, accounting for 5.7%–7.6% of all malignancies, and there is an upward trend in the incidence rate of this disease [1, 2]. e mortality and recurrence rates are still high after surgery, radiotherapy, and chemotherapy
H42021700), cisplatin (DDP) injection (Jiangsu Hausen Pharmaceutical Co., Ltd., Chinese pharmaceutical standard no. 20040813), a chemiluminescence imaging system (Bio-Rad, CA, USA), monoclonal antibodies against Signal transducer and activator of transcription 3 (STAT3), p-STAT3, cyclin D1, P27, and GAPDH (Cell Signalling Technology, Inc., Danvers, MA, USA), PCR primers (Shanghai Zhenzhi Biology Co., Ltd., Shanghai, China), phenol-free red RPMI, pancreatin, PBS, serum (Gibco, Australia), a thermometer, and a 1 ml syringe were used among other materials
We aimed to guarantee the repeatability of future experiments by ensuring the quality and stability of Erchen plus Huiyanzhuyu decoction (EHD). e active components of EHD and their concentrations were analysed by HPLC

Summary

Introduction

Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumour of head and neck cancer, accounting for 5.7%–7.6% of all malignancies, and there is an upward trend in the incidence rate of this disease [1, 2]. e mortality and recurrence rates are still high after surgery, radiotherapy, and chemotherapy. Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumour of head and neck cancer, accounting for 5.7%–7.6% of all malignancies, and there is an upward trend in the incidence rate of this disease [1, 2]. E main effect of Erchen plus Huiyanzhuyu decoction (EHD) is Evidence-Based Complementary and Alternative Medicine to remove phlegm and blood stasis, and EHD has achieved satisfactory clinical results. It consists of two classic decoctions, Erchen decoction (ECD) and Huiyanzhuyu decoction (HYZYD). We previously found that modified EHD could relieve symptoms, improve recovery, and reduce the recurrence of precancerous lesions of LC diseases, including laryngeal papilloma and laryngeal leukoplakia [13]

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