Cediranib Induces Apoptosis, G1 Phase Cell Cycle Arrest, and Autophagy in Non-Small-Cell Lung Cancer Cell A549 In Vitro.

Menghuan Guo,Zhong Guo,Zhiyuan Liu,Jin Zhao,Lu Gan,Hong Zhang,Jing Si,Jinhua Zhang,Yi Xie,Ning Cao

doi:10.1155/2021/5582648

Abstract

Lung cancer remains the leading cause of cancer death worldwide. Late diagnosis, chemoresistance, and metastasis are the main reasons for the high mortality rate of lung cancer. Therefore, the development of other treatments is urgent. Cediranib (CED), a vascular endothelial growth factor receptor (VEGFR) kinase inhibitor, shows promising antitumour activities in various cancers including lung cancer. Here, we explored the effects and the underlying molecular mechanism of CED on non-small-cell lung cancer (NSCLC) cell line A549 cells in vitro. Our results show that CED could inhibit A549 cell proliferation and cloning formation. Meanwhile, G1 phase cell cycle arrest was also found, as featured by the increased proportion of G1 phase cells as well as the reduction of G1 phase relative proteins CDK4/cyclin D1 and CDK2/cyclin E. Moreover, the ratio of LC3-II/LC3-I was elevated significantly in CED-treated groups compared with the controls. Furthermore, the expression of p-Akt, p-P38, p-Erk1/2, and p-mTOR proteins was decreased obviously in the treatment groups. These results suggest that CED could induce apoptosis and G1 phase cell cycle arrest in A549 cells. Meanwhile, CED may induce autophagy through MAPK/Erk1/2 and Akt/mTOR signal pathway in A549 cells.

Highlights

Lung cancer is one of the most common malignancies and ranks the 1st in both incidence and mortality, with approximately 2.09 million new cases and 1.76 million deaths in the world in 2018 according to the Internal Agency for Research on Cancer
vascular endothelial growth factor receptor (VEGFR) inhibitors such as Ramucirumab have improved the prognosis of patients with non-small-cell lung cancer (NSCLC) [5], suggesting that VEGFR inhibitor is a new strategy for NSCLC treatment
The Cell counting kit-8 (CCK-8) assay showed that CED could markedly inhibit the growth of A549 cells in a concentration- and time-dependent manner

Summary

Introduction

Lung cancer is one of the most common malignancies and ranks the 1st in both incidence and mortality, with approximately 2.09 million new cases and 1.76 million deaths in the world in 2018 according to the Internal Agency for Research on Cancer. NSCLC accounts for approximately 80-85% of all lung cancers, and the 5-year survival rate for NSCLC patients was less than 15% currently [1, 2]. 80% patients with NSCLC develop metastases within 2 years after the diagnosis of NSCLC. Diagnosis of lung cancer before clinical symptoms is an effective means to reduce cancer mortality, and the use of low-dose CT scans contributes to a 20% reduction in lung cancer mortality according to National Lung Screening Trial [3]. Over 60% of patients are diagnosed with lung cancer in the advanced stages [4]. VEGFR inhibitors such as Ramucirumab have improved the prognosis of patients with NSCLC [5], suggesting that VEGFR inhibitor is a new strategy for NSCLC treatment

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