Selective β2-AR Blockage Suppresses Colorectal Cancer Growth Through Regulation of EGFR-Akt/ERK1/2 Signaling, G1-Phase Arrest, and Apoptosis
| Autor: | Chih-Chien, Chin, Jhy-Ming, Li, Kam-Fai, Lee, Yun-Ching, Huang, Kuan-Chieh, Wang, Hsiao-Ching, Lai, Chih-Chung, Cheng, Yi-Hung, Kuo, Chung-Sheng, Shi |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Cell Survival MAP Kinase Signaling System Gene Expression Mice Nude Apoptosis Cell Cycle Proteins Propanolamines Mice Adrenergic beta-2 Receptor Antagonists Cell Line Tumor Receptors Adrenergic beta Animals Humans Cytochromes c HCT116 Cells Adrenergic beta-1 Receptor Antagonists G1 Phase Cell Cycle Checkpoints Propranolol Xenograft Model Antitumor Assays ErbB Receptors Atenolol Proto-Oncogene Proteins c-bcl-2 Colorectal Neoplasms HT29 Cells Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Journal of cellular physiology. 231(2) |
| ISSN: | 1097-4652 |
| Popis: | The stress-upregulated catecholamines-activated β1- and β2-adrenergic receptors (β1/2-ARs) have been shown to accelerate the progression of cancers such as colorectal cancer (CRC). We investigated the underlying mechanism of the inhibition of β1/2-ARs signaling for the treatment of CRC and elucidated the significance of β2-AR expression in CRC in vitro and in clinical samples. The impacts of β1/2-AR antagonists in CRC in vitro and CRC-xenograft in vivo were examined. We found that repression of β2-AR but not β1-AR signaling selectively suppressed cell viability, induced G1-phase cell cycle arrest, caused both intrinsic and extrinsic pathways-mediated apoptosis of specific CRC cells and inhibited CRC-xenograft growth in vivo. Moreover, the expression of β2-AR was not consistent with the progression of CRC in vitro or in clinical samples. Our data evidence that the expression profiles, signaling, and blockage of β2-AR have a unique pattern in CRC comparing to other cancers. β2-AR antagonism selectively suppresses the growth of CRC accompanying active β2-AR signaling, which potentially carries wild-type KRAS, in vitro and in vivo via the inhibition of β2-AR transactivated EFGR-Akt/ERK1/2 signaling pathway. Thus, β2-AR blockage might be a potential therapeutic strategy for combating the progressions of β2-AR-dependent CRC. |
| Databáze: | OpenAIRE |
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