T-type Ca2+ channel blocker, KYS05047 induces G1 phase cell cycle arrest by decreasing intracellular Ca2+ levels in human lung adenocarcinoma A549 cells

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.

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PTENInhibits Cell Proliferation, Promotes Cell Apoptosis, and Induces Cell Cycle Arrest via Downregulating the PI3K/AKT/hTERTPathway in Lung Adenocarcinoma A549 Cells

BioMed Research International ◽

10.1155/2016/2476842 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 31

Author(s):

Xiao-Xiao Lu ◽

Lan-Yu Cao ◽

Xi Chen ◽

Jian Xiao ◽

Yong Zou ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Lung Adenocarcinoma ◽

Cell Cycle Arrest ◽

Cell Apoptosis ◽

A549 Cells ◽

Akt Pathway ◽

Wild Type ◽

Cycle Arrest ◽

Lung Adenocarcinoma A549

PTENplays an essential role in tumorigenesis and both its mutation and inactivation can influence proliferation, apoptosis, and cell cycle progression in tumor cells. However, the precise role ofPTENin lung cancer cells has not been well studied. To address this, we have generated lung adenocarcinoma A549 cells overexpressing wild-type or mutantPTENas well as A549 cells expressing a siRNA directed toward endogenousPTEN. Overexpression of wild-typePTENprofoundly inhibited cell proliferation, promoted cell apoptosis, caused cell cycle arrest at G1, downregulated p-AKT, and decreased expression of the telomerase proteinhTERT. In contrast, in cells expressing aPTENdirected siRNA, the opposite effects on cell proliferation, apoptosis, cell cycle arrest, p-AKT levels, andhTERTprotein expression were observed. A549 cells transfected with aPTENmutant lacking phosphatase activity (PTEN-C124A) or an empty vector (null) did not show any effect. Furthermore, using the PI3K/AKT pathway blocker LY294002, we confirmed that the PI3K/AKT pathway was involved in mediating these effects ofPTEN. Taken together, we have demonstrated thatPTENdownregulates the PI3K/AKT/hTERTpathway, thereby suppressing the growth of lung adenocarcinoma cells. Our study may provide evidence for a promising therapeutic target for the treatment of lung adenocarcinoma.

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