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

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.

P53-Independent G1-Cell Cycle Arrest Increases SARS-CoV-2 RNA Replication

“…Having found that G0/G1 cell cycle arrest was responsible for the increasing in SARS-CoV-2 RNA replication, we next focused on the cellular pathways involved in the G0/G1 stage ( Figure 5 A) in order to understand which pathways are important for SARS-CoV-2 replication. To do this, we used several compounds that are known to block the cell cycle in G0/G1 in A549 cells (Palbociclib [ 25 ], Abemaciclib [ 26 , 27 ], Gefitinib [ 28 ], Cediranib [ 29 ], Resveratrol [ 30 ], and Hesperidin [ 31 ]). These compounds target different pathways described in Figure 5 B. Inhibitors of growth factor receptors (EGFR and VEGFR) tyrosine kinase (Gefitinib and Cediranib) led to an increase in SARS-CoV-2 infection ( Figure 5 C).…”

Apatinib plus docetaxel or pemetrexed shows promising activities against non-small cell lung cancer with brain metastasis: a retrospective analysis

“…Originally, apatinib was regarded as an anti-angiogenesis inhibitor against VEGFR-2, similar to drugs of a similar type, namely, sorafenib, sunitinib, and cabozantinib ( 31 ). Considering the limited efficiency of other anti-angiogenesis inhibitors, such as cediranib ( 32 ) in advanced NSCLC, it is rather possible that mechanism of apatinib may be different ( 33 ). Apatinib may also possess other targets, such as RET, FlT3, and so on ( 34 ).…”

Regulation of apoptosis, autophagy and ferroptosis by non‑coding RNAs in metastatic non‑small cell lung cancer (Review)

“…Combined therapy with rapamycin and suberoylanilide hydroxamic acid may also increase radiosensitivity in these cells and inhibiting the levels of autophagy can markedly weaken the radiotherapy sensitivity caused by this combined treatment, thus suggesting that the inhibitory effect of combination therapy may be partially due to the induction of autophagy in NSCLC ( 79 ). Cediranib has also been shown to exhibit effective anti-tumor activities in NSCLC cells by inducing G 1 phase cell cycle arrest and autophagy via the MAPK/Erk1/2 and Akt/mTOR pathways in A549 cells ( 80 ).…”