Combination of Cordycepin and Apatinib Synergistically Inhibits NSCLC Cells by Down-Regulating VEGF/PI3K/Akt Signaling Pathway.

Xiaozhong Liao,Jue Zhang,Hanrui Chen,Zhuo-Xun Wu,Lanting Tao,Lingling Sun,Wei Guo,Lizhu Lin,Jing Wang,Haiyan Du,Zhe-Sheng Chen

doi:10.3389/fonc.2020.01732

Abstract

BackgroundThe application of apatinib is immensely limited by its acquired drug resistance. This research investigates whether cordycepin, a component from Cordyceps could synergize with apatinib to improve its anticancer effect on non-small cell lung cancer (NSCLC) cells.MethodsThe NSCLC cell lines A549, PC9, and H1993, and human bronchial epithelial (HBE) cell line Bears-2B were used in this study. Cell counting kit 8, colony formation assays, wound healing assay, transwell assay, and flow cytometry analysis were performed to assess the cell viability, the migration ability, and invasion ability of the cells. Kyoto encyclopedia of genes and genomes (KEGG), western blotting and molecular docking was applied to analyze the possible pathways affected by cordycepin.ResultsThe combination of cordycepin and apatinib in a ratio of 5:1 synergistically reduced proliferation of NSCLC cells, inhibited cell migration and invasion, increased cell apoptosis by altering cell cycle in NSCLC A549 and PC9 cells. The VEGF/PI3K/Akt pathway was inhibited after treatment with cordycepin and apatinib.ConclusionOur findings demonstrated that the combination of cordycepin and apatinib has synergistically anticancer effect on NSCLC cells by down-regulating VEGF/PI3K/Akt signaling pathway. This result indicated that cordycepin and apatinib could be a promising drug combination against NSCLC.

Highlights

Lung cancer is one of the cancers with high morbidity and mortality, which consists of more than 50 histological subtypes [1, 2]
The aim of this study is to investigate whether cordycepin and apatinib have synergistic anticancer effect on human Non-small cell lung cancer (NSCLC) cells, and the potential signaling pathway related to this effect by a series of molecular biology methods
It was found that both cordycepin and apatinib inhibited the growth of NSCLC cells and human bronchial epithelial (HBE) cells in a dosage- and timedependent manner

Summary

Introduction

Lung cancer is one of the cancers with high morbidity and mortality, which consists of more than 50 histological subtypes [1, 2]. Cordycepin and Apatinib Inhibits NSCLC induced by such treatments seriously impair the prognosis of cancer patients. It was confirmed that apatinib can be used as subsequent-line treatment for other advanced or metastatic solid tumors, such as NSCLC, breast cancer and hepatocellular carcinoma (HCC) [6]. An increasing number of clinical trials have reported that apatinib has potential benefits in the treatment of patients with advanced NSCLC [7,8,9]. The application of apatinib is limited by the emergence of acquired resistance and side effects including hypertension and hand-foot syndrome [11]. This research investigates whether cordycepin, a component from Cordyceps could synergize with apatinib to improve its anticancer effect on non-small cell lung cancer (NSCLC) cells

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