Antiangiogenesis Roles of Exosomes with Fei-Liu-Ping Ointment Treatment are Involved in the Lung Carcinoma with the Lewis Xenograft Mouse Model.

Qi Zheng,Wei Hou,Huiting Fan,Ying Zhang,Haolong Liu

doi:10.1155/2020/9418593

Abstract

Exosomes display efficient biocompatibility and represent valuable vehicles for drug or effective material delivery in a tumour-therapeutic approach. Following treatment with Fei-Liu-Ping (FLP) ointment, a traditional Chinese herbal formula, which is used for treating lung cancer patients, could inhibit lung carcinoma growth in clinical and animal studies. In the present study, the values of VEGF and PDGF, which were closely related to angiogenesis, were estimated in serum and carcinoma tissue exosomes to unveil the FLP effects on angiogenesis. The common inflammatory factors of IL-6, IL-1β, TNF-α, and TGF-β in serum exosomes were also detected with the Lewis xenograft model. Methods. Male C57BL/6 mice were randomly divided into four groups, namely, normal, model, cyclophosphamide (CTX), and FLP treatment groups. Histological structures were observed and imaged by H&E. CD31 expressions in tumour tissues were detected by immunofluorescence (IF) and western blot (WB). VEGF, PDGF, and PDGFR levels in exosomes, serum, tumour, and lung tissues were detected by enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), and WB, respectively. IL-6, IL-1β, TNF-α, and TGF-β levels in exosomes were measured by multiplex immunoassay panels. Results. The results showed that FLP had tumour growth inhibition rate (39.31%). CD31 protein expression was obviously decreased in tumour tissues of CTX- and FLP-treated MO mice, compared to that of MO mice (P < 0.05 or P < 0.001). VEGF, PDGF, and PDGFR expression levels with FLP treatment were downregulated in exosomes, serum, tumour, and lung tissues compared to model group (P < 0.05 or P < 0.01). The expressions of IL-6, IL-1β, and TNF-α were downregulated in exosomes compared to the model group (P < 0.05 or P < 0.01). Conclusions. This study suggested that FLP had the ability of inhibiting tumourigenesis in a Lewis lung xenograft mouse model, whose therapeutic mechanisms might relate with the downregulation of angiogenesis factor and tumour inflammatory cytokines levels.

Highlights

Lung carcinoma is the most frequent lethal malignancy and the leading cause of cancer death worldwide, harbouring high incidence in Asian countries [1, 2]
Based on the abovementioned results, we found that FLP ointment could inhibit the tumour growth of Lewis lung cancer cells
We examined the expression of CD63 and Alix proteins in the normal control (NC)-EXOs, MO-EXOs, and FLP-EXOs, which expressed these proteins. e present study found that FLP ointment could increase CD63 and Alix protein levels compared to those of MO mice, which illustrated that FLP ointment could interfere exosomes in serum

Summary

Introduction

Lung carcinoma is the most frequent lethal malignancy and the leading cause of cancer death worldwide, harbouring high incidence in Asian countries [1, 2]. Traditional Chinese medicine (TCM) has been shown to be effective in the treatment of lung cancer, especially in decreasing the risk of tumour recurrence and metastasis [6, 7]. Using systematic reviews and meta-analyses, scholars have recently reported that Chinese herbal medicine could improve survival, quality of life, and immune suppression and reduce tumour recurrence and metastasis in lung cancer patients by alleviating immune suppression [7, 8]. Previous clinical studies have shown that FLP ointment possessed many marked anticancer properties, such as relieving the manifested symptoms, ameliorating the side effects of radiotherapy and chemotherapy, and reducing the dose of medication required, improving the quality of life in lung cancer patients [8,9,10]. Exosomes are tens nm in size, which allows genetic and molecular exchanges, including the transfer of proteins such as VEGF, PDGF, and PDGFR at a distance to target cells

Materials and Methods

Findings

Results