Targeted inhibition of the phosphoinositide 3-kinase impairs cell proliferation, survival, and invasion in colon cancer
| Autor: | Fei Yang, Zhen-Hua Du, Wei Gao, Hua Chen, Xue-Qun Zhang, Jun-Yi Gao |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Colorectal cancer Caspase 3 OncoTargets and Therapy PI3KCA knockdown 03 medical and health sciences 0302 clinical medicine medicine Pharmacology (medical) Protein kinase B PI3K/AKT/mTOR pathway Original Research Phosphoinositide 3-kinase biology Cell growth Chemistry Cancer human colon cancer BEZ235 medicine.disease PI3K/Akt/mTOR pathway 030104 developmental biology Oncology Apoptosis 030220 oncology & carcinogenesis biology.protein Cancer research |
| Zdroj: | OncoTargets and therapy |
| ISSN: | 1178-6930 |
| DOI: | 10.2147/ott.s145601 |
| Popis: | Fei Yang,1,* Jun-Yi Gao,2,* Hua Chen,1 Zhen-Hua Du,1 Xue-Qun Zhang,3 Wei Gao4 1Department of Pathology, Jinan Central Hospital Affiliated to Shandong University, Jinan, 2Department of Clinical Medicine, Weifang Medical College, Weifang, 3Graduate School, Taishan Medical University, Xintai, 4Department of Oncology, Jinan Central Hospital Affiliated to Shandong University, Jinan, People’s Republic of China *These authors contributed equally tothis work 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. Keywords: human colon cancer, PI3K/Akt/mTOR pathway, BEZ235, PI3KCA knockdown |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|