Targeted Inhibition of the Phosphoinositide 3-kinase Impairs Cell Proliferation, Survival, and Invasion in Colon Cancer

Overview

Journal Onco Targets Ther

Publisher Dove Medical Press

Specialty Oncology

Date 2017 Oct 6

PMID 28979133

Citations 13

Authors

Fei Yang

Jun-Yi Gao

Hua Chen

Zhen-Hua Du

Xue-Qun Zhang

Wei Gao

Affiliations

Soon will be listed here.

Abstract

Background: Colon cancer is the third most common cancer in the world, and its metastasis and drug resistance are challenging for its effective treatment. The PI3K/Akt/mTOR pathway plays a crucial role in the pathogenesis of colon cancer. The aim of this study was to investigate the targeting of PI3K in colon cancer cells HT-29 and HCT-116 in vitro.

Methods: In HT-29 and HCT-116 cells, BEZ235, a dual inhibitor of PI3K/mTOR, and shRNAtarget to PI3KCA were used to inhibit PI3K/Akt/mTOR pathway. The inhibition efficiency of PI3K/Akt/mTOR pathway was detected by RT-PCR and Western blot. Cell proliferation, migration, invasion, and apoptosis were evaluated by Cell Counting Kit-8, Transwell, and flow cytometry assays. The expression of apoptosis-related proteins (cleavage caspase 3, Bcl-2, Bax, and Bim) were also detected.

Results: We found that in HT-29 and HCT-116 cells, the treatment of BEZ235 (1 μM) and PI3KCA knockdown inhibited the activation of PI3K/Akt/mTOR pathway and significantly suppressed cell proliferation, migration, and invasion of HT-29 and HCT-116 cells. In addition, we confirmed that knockdown of BEZ235 and PI3KCA induced cell apoptosis through the upregulated levels of cleavage caspase 3 and Bax and downregulated expression of Bcl-2 and Bim.

Conclusion: Our results indicated that targeted inhibition of the PI3K/Akt/mTOR pathway impaired cell proliferation, survival, and invasion in human colon cancer.

Citing Articles

Identification and Validation of Key miRNAs for Colon Cancer Based on miRNA-Gene Integration Analysis.

Ji Y, Gu J, Zhang H, Xu H Int J Gen Med. 2023; 16:5703-5718.

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Mechanism of anticancer effect of ETP-45658, a PI3K/AKT/mTOR pathway inhibitor on HT-29 Cells.

Yulak F, Filiz A, Joha Z, Ergul M Med Oncol. 2023; 40(12):341.

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Survival of HT29 cancer cells is influenced by hepatocyte growth factor receptor inhibition through modulation of self-DNA-triggered TLR9-dependent autophagy response.

Bohusne Barta B, Simon A, Nagy L, Danko T, Raffay R, Petovari G PLoS One. 2022; 17(5):e0268217.

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Chen Y, Lai Y, Hsuuw Y, Chang K Int J Mol Sci. 2021; 22(7).

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