MK615 inhibits pancreatic cancer cell growth by dual inhibition of Aurora A and B kinases

作     者：Toshie Okada Tokihiko Sawada Tatsushi Osawa Masakazu Adachi Keiichi Kubota 

作者机构：Second Department of Surgery Dokkyo University School of Medicine Kitakobayashi 880MibuShimotsugaTochigi 321-0293Japan Second Department of SurgeryDokkyo University School of Medicine Kitakobayashi 880MibuShimotsuga Tochigi 321-0293Japan Japan Apricot Co.Ltd.1-11-7 MidorichoTakasakiGunma 370-0073 Japan Japan ApricotCo. Ltd.1-11-7 MidorichoTakasakiGunma 370-0073 Japan Second Department of SurgeryDokkyo University School of MedicineKitakobayashi 880Mibu ShimotsugaTochigi 321-0293Japan 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2008年第14卷第9期

页      面：1378-1382页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主　　题：Japanese apricot Aurora kinases Pancreatic cancer Cell cycle 

摘      要：AIM:To investigate the anti-neoplastic effect of MK615, an anti-neoplastic compound isolated from Japanese apricot, against human pancreatic cancer cells in vitro. METHODS: Three human pancreatic cancer cell lines PANC-1, PK-1, and PK45H were cultured with MK615 at concentrations of 600, 300, 150, and 0 μg/mL. Growth inhibition was evaluated by cell proliferation assay, and killing activity was determined by lactate dehydrogenase (LDH) assay. Expression of Aurora A and B kinases was detected by real-time polymerase chain reaction (PCR) and Western blotting. Cell cycle stages were evaluated by flow cytometry. RESULTS: The growth inhibitory rates of MK615 at 150, 300, and 600 μg/mL were 2.3% ± 0.9%, 8.9% ± 3.2% and 67.1% ± 8.1% on PANC1 cells, 1.3% ± 0.3%, 8.7% ± 4.1% and 45.7 ± 7.6% on PK1 cells, and 1.2 ± 0.8%, 9.1% ± 2.1% and 52.1% ± 5.5% on PK45H cells, respectively (P 0.05). The percentage cytotoxicities of MK615 at 0, 150, 300, and 600 μg/mL were 19.6% ± 1.3%, 26.7% ± 1.8%, 25.5% ± 0.9% and 26.4% ± 0.9% in PANC1 cells, 19.7% ± 1.3%, 24.7% ± 0.8%, 25.9% ± 0.9% and 29.9% ± 1.1% in PK1 cells, and 28.0% ± 0.9%, 31.2% ± 0.9%, 30.4% ± 1.1% and 35.3 ± 1.0% in PK45H cells, respectively (P 0.05). Real-time PCR and Western blotting showed that MK615 dually inhibited the expression of Aurora A and B kinases. Cell cycle analysis revealed that MK615 increased the population of cells in G2/M phase. CONCLUSION: MK615 exerts an anti-neoplastic effect on human pancreatic cancer cells in vitro by dual inhibition of Aurora A and B kinases.