Depletion of PI3K p85α induces cell cycle arrest and apoptosis in colorectal cancer cells
| Autor: | Yu-gang Song, Xiao-yun Xie, Fa-man Xiao, Yan Sun, Kang Li, Hua Tian, Shi-Yi Zhao |
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| Rok vydání: | 2009 |
| Předmět: |
Cancer Research
medicine.medical_specialty Deleted in Colorectal Cancer Cell growth Cancer General Medicine Mouse model of colorectal and intestinal cancer Cell cycle Biology medicine.disease_cause medicine.disease Intracellular signal transduction Endocrinology Oncology Internal medicine medicine Cancer research Carcinogenesis hormones hormone substitutes and hormone antagonists PI3K/AKT/mTOR pathway |
| Zdroj: | Oncology Reports. 22 |
| ISSN: | 1021-335X |
| Popis: | Colorectal cancer is one of the most common malignancies in the world. Overactivity of phosphatidylinositol 3-kinase (PI3K) is frequently detected in colorectal carcinoma. PI3K signaling plays a pivotal role in intracellular signal transduction pathways involved in cell growth, cellular transformation, and tumorigenesis. To specifically inhibit PI3K activity in colorectal cancer cells, we constructed a siRNA against the PI3K regulatory subunit p85alpha and transfected it into LoVo and SW480 cells. In the present study, treatment of colorectal cancer cells with PI3K p85alpha-specific siRNA inhibited cell proliferation, induced G1 phase cell cycle arrest and sensitized colorectal cancer cells to 5-FU-induced apoptosis. Furthermore, depletion of PI3K p85alpha resulted in significant activation of three Forkhead box class O (FoxO) transcription factors, which inhibited the expression of cyclin D1, cdk4 and induced expression of p27/Kip1. Activation of FoxO transcription factors also increased the expression of FasL. Thus, our results indicate that siRNA-mediated gene silencing of PI3K p85alpha may be a useful therapeutic strategy for colorectal carcinoma. |
| Databáze: | OpenAIRE |
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