title: Sildenafil inhibits the growth of human colorectal cancer in vitro and in vivo.
abstract: Colorectal cancer is the third most common human cancer with frequent overexpression of the cGMP-specific phosphodiesterase 5 (PDE5). In the present study, we investigated that the anticancer effect of sildenafil on human colorectal cancer in vitro and in vivo, which is a potent and selective inhibitor of PDE5 for the treatment of erectile dysfunction and pulmonary arterial hypertension in the clinic. Sildenafil significantly induced cell growth inhibition, cell cycle arrest and apoptosis of human colorectal cancer with increased intracellular reactive oxidative specie (ROS) levels, which were accompanied by obvious alterations of related proteins such as CDKs, Cyclins and PARP etc. Pretreatment with ROS scavenger N-acetyl-L-cysteine could reverse sildenafil-induced ROS accumulation and cell apoptosis. Inhibition of the activity of protein kinase G with KT-5823 could enhance sildenafil-induced apoptosis. Furthermore, sildenafil caused the reduction of xenograft models of human colorectal cancer in nude mice. Overall, these findings suggest that sildenafil has the potential to be used for treatment of human colorectal cancer.
authors.affiliation: Department of Cell Biology and Institute of Biomedicine, College of Life Science and Technology, Jinan University, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine Guangzhou 510632, Guangdong, China.
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Mei
authors.affiliation: Department of Cell Biology and Institute of Biomedicine, College of Life Science and Technology, Jinan University, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine Guangzhou 510632, Guangdong, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Hepatobiliary Surgery, Cancer Center, Sun Yat-sen University Guangzhou 510060, Guangdong, China.
authors.forename: Yao-Jun
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: Department of Gastrointertinal Surgery and General Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences Guangzhou 510080, Guangdong, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou 510060, Guangdong, China.
authors.forename: Jin-Ming
authors.initials: JM
authors.lastname: Zhao
authors.affiliation: Department of Cell Biology and Institute of Biomedicine, College of Life Science and Technology, Jinan University, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine Guangzhou 510632, Guangdong, China.
authors.forename: Jian-Ge
authors.initials: JG
authors.lastname: Qiu
authors.affiliation: Department of Cell Biology and Institute of Biomedicine, College of Life Science and Technology, Jinan University, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine Guangzhou 510632, Guangdong, China.
authors.forename: Wen-Ji
authors.initials: WJ
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology and Institute of Biomedicine, College of Life Science and Technology, Jinan University, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine Guangzhou 510632, Guangdong, China.
authors.forename: Qi-Wei
authors.initials: QW
authors.lastname: Jiang
authors.affiliation: Department of Cell Biology and Institute of Biomedicine, College of Life Science and Technology, Jinan University, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine Guangzhou 510632, Guangdong, China.
authors.forename: You-Qiu
authors.initials: YQ
authors.lastname: Xue
authors.affiliation: Department of Cell Biology and Institute of Biomedicine, College of Life Science and Technology, Jinan University, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine Guangzhou 510632, Guangdong, China.
authors.forename: Di-Wei
authors.initials: DW
authors.lastname: Zheng
authors.affiliation: Department of Cell Biology and Institute of Biomedicine, College of Life Science and Technology, Jinan University, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine Guangzhou 510632, Guangdong, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Cell Biology and Institute of Biomedicine, College of Life Science and Technology, Jinan University, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine Guangzhou 510632, Guangdong, China.
authors.forename: Wu-Ming
authors.initials: WM
authors.lastname: Qin
authors.affiliation: Department of Cell Biology and Institute of Biomedicine, College of Life Science and Technology, Jinan University, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine Guangzhou 510632, Guangdong, China.
authors.forename: Meng-Ning
authors.initials: MN
authors.lastname: Wei
authors.affiliation: Department of Cell Biology and Institute of Biomedicine, College of Life Science and Technology, Jinan University, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine Guangzhou 510632, Guangdong, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Shi
keywords: PDE5; PKG; Sildenafil; colorectal cancer