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J Cell Physiol. 2016 Feb;231(2):459-72. doi: 10.1002/jcp.25092. Epub 2015 Sep 1.

Selective β2-AR Blockage Suppresses Colorectal Cancer Growth Through Regulation of EGFR-Akt/ERK1/2 Signaling, G1-Phase Arrest, and Apoptosis.

Author information

1
Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
2
Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan.
3
Department of Anatomic Pathology, Chang Gung Memorial Hospital, Chiayi, Taiwan.
4
Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan.

Abstract

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.

PMID:
26189563
DOI:
10.1002/jcp.25092
[Indexed for MEDLINE]

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