title: Statin induces apoptosis of human colon cancer cells and downregulation of insulin-like growth factor 1 receptor via proapoptotic ERK activation.
abstract: Insulin-like growth factor 1 (IGF-1) and IGF-1 receptor (IGF-1R) signaling plays an important role in tumor progression in patients with certain gastrointestinal tract cancers. In addition to lowering cholesterol in serum, statins have pleiotropic effects, including anti-oxidative, anti-inflammatory or anti-neoplastic effects. Therefore, the present study investigated whether statins could induce the apoptosis of colon cancer cells and regulate the expression of IGF-1R and its associated signaling pathways in the present study. It was demonstrated that simvastatin and pravastatin suppressed cell proliferation and induced cell death in human HT-29 cells, but simvastatin was more potent than pravastatin. Simvastatin induced apoptosis in a concentration-dependent manner. In addition, simvastatin suppressed the expression of IGF-1R and inhibited the activity of phosphorylated-extracellular signal-regulated kinase (ERK)1/2 and phosphorylated-Akt activated by IGF-1. Simvastatin and IGF-1 each stimulated the activity of phosphorylated ERK1/2. However, simvastatin inhibited cell proliferation and IGF-1 stimulated cell proliferation. Mevalonic acid and PD98059 reversed the ERK activation and apoptosis induced by treatment with simvastatin. It was concluded that simvastatin induces the apoptosis of human colon cancer cells and inhibits IGF-1-induced ERK and Akt expression via the downregulation of IGF-1R expression and proapoptotic ERK activation. Simvastatin may be beneficial for the treatment of colon cancer. The present study suggested that statin may possess therapeutic potential for the treatment of colon cancer.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Dongtan Sacred Heart Hospital, Hallym University School of Medicine, Hwasung, Gyeonggi 445-170, Republic of Korea.
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Jang
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Dongtan Sacred Heart Hospital, Hallym University School of Medicine, Hwasung, Gyeonggi 445-170, Republic of Korea.
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Hong
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Dongtan Sacred Heart Hospital, Hallym University School of Medicine, Hwasung, Gyeonggi 445-170, Republic of Korea.
authors.forename: Se Woo
authors.initials: SW
authors.lastname: Park
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Dongtan Sacred Heart Hospital, Hallym University School of Medicine, Hwasung, Gyeonggi 445-170, Republic of Korea.
authors.forename: Hyun Woo
authors.initials: HW
authors.lastname: Byun
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Dongtan Sacred Heart Hospital, Hallym University School of Medicine, Hwasung, Gyeonggi 445-170, Republic of Korea.
authors.forename: Dong Hee
authors.initials: DH
authors.lastname: Koh
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Dongtan Sacred Heart Hospital, Hallym University School of Medicine, Hwasung, Gyeonggi 445-170, Republic of Korea.
authors.forename: Min Ho
authors.initials: MH
authors.lastname: Choi
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Dongtan Sacred Heart Hospital, Hallym University School of Medicine, Hwasung, Gyeonggi 445-170, Republic of Korea.
authors.forename: Sea Hyub
authors.initials: SH
authors.lastname: Kae
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Dongtan Sacred Heart Hospital, Hallym University School of Medicine, Hwasung, Gyeonggi 445-170, Republic of Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Lee
keywords: ERK; apoptosis; colon cancer; insulin-like growth factor-1; statin