title: Synergistic Effects of Simvastatin and Irinotecan against Colon Cancer Cells with or without Irinotecan Resistance.
abstract: Aims. We here investigated whether the combination of simvastatin and irinotecan could induce the synergistic effect on colon cancer cells with or without resistance to irinotecan. Methods. We investigated cell proliferation assay and assessed cell death detection ELISA and caspase-3 activity assay of various concentrations of simvastatin and irinotecan to evaluate the efficacy of drug combination on colon cancer cells with or without irinotecan resistance. Results. The IC50 values of simvastatin alone and irinotecan alone were 115.4 ± 0.14 μM (r = 0.98) and 62.5 ± 0.18 μM (r = 0.98) in HT-29 cells without resistance to irinotecan. The IC50 values of these two drugs were 221.9 ± 0.22 μM (r = 0.98) and 195.9 ± 0.16 μM (r = 0.99), respectively, in HT-29 cell with resistance to irinotecan. The results of combinations of the various concentrations of two drugs showed that combined treatment with irinotecan and simvastatin more efficiently suppressed cell proliferation of HT-29 cells even with resistance to irinotecan as well as without resistance. Furthermore, the combination of simvastatin and irinotecan at 2 : 1 molar ratio showed the best synergistic interaction. Conclusion. Simvastatin could act synergistically with irinotecan to overcome irinotecan resistance of colon cancer.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Dongtan Sacred Heart Hospital, Hallym University School of Medicine, Gyeonggi-do 18450, 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, Gyeonggi-do 18450, 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, Gyeonggi-do 18450, Republic of Korea.
authors.forename: Juah
authors.initials: J
authors.lastname: Jang
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Dongtan Sacred Heart Hospital, Hallym University School of Medicine, Gyeonggi-do 18450, Republic of Korea.
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Choi
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Dongtan Sacred Heart Hospital, Hallym University School of Medicine, Gyeonggi-do 18450, Republic of Korea.
authors.forename: Se Woo
authors.initials: SW
authors.lastname: Park
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hangang Sacred Heart Hospital, Hallym University School of Medicine, Seoul, 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, Gyeonggi-do 18450, 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, Gyeonggi-do 18450, 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, Gyeonggi-do 18450, 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, Gyeonggi-do 18450, Republic of Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Lee