MK615通过双重抑制极光激酶A和B来抑制胰腺癌细胞生长。
MK615 inhibits pancreatic cancer cell growth by dual inhibition of Aurora A and B kinases.
作者信息
Okada Toshie, Sawada Tokihiko, Osawa Tatsushi, Adachi Masakazu, Kubota Keiichi
机构信息
Second Department of Surgery, Dokkyo University School of Medicine, Kitakobayashi 880, Mibu, Shimotsuga, Tochigi 321-0293, Japan.
出版信息
World J Gastroenterol. 2008 Mar 7;14(9):1378-82. doi: 10.3748/wjg.14.1378.
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 microg/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 microg/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 microg/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.
目的
研究从日本杏中分离得到的抗肿瘤化合物MK615对人胰腺癌细胞的体外抗肿瘤作用。
方法
将三种人胰腺癌细胞系PANC-1、PK-1和PK45H分别用浓度为600、300、150和0微克/毫升的MK615进行培养。通过细胞增殖试验评估生长抑制情况，通过乳酸脱氢酶（LDH）试验测定杀伤活性。通过实时聚合酶链反应（PCR）和蛋白质免疫印迹法检测极光激酶A和B的表达。通过流式细胞术评估细胞周期阶段。
结果
MK615在150、300和600微克/毫升时对PANC1细胞的生长抑制率分别为2.3%±0.9%、8.9%±3.2%和67.1%±8.1%，对PK1细胞的生长抑制率分别为1.3%±0.3%、8.7%±4.1%和45.7%±7.6%，对PK45H细胞的生长抑制率分别为1.2%±0.8%、9.1%±2.1%和52.1%±5.5%（P<0.05）。MK615在0、150、300和600微克/毫升时对PANC1细胞的细胞毒性百分比分别为19.6%±1.3%、26.7%±1.8%、25.5%±0.9%和26.4%±0.9%，对PK1细胞的细胞毒性百分比分别为19.7%±1.3%、24.7%±0.8%、25.9%±0.9%和29.9%±1.1%，对PK45H细胞的细胞毒性百分比分别为28.0%±0.9%、31.2%±0.9%、30.4%±1.1%和35.3%±1.0%（P<0.05）。实时PCR和蛋白质免疫印迹法显示，MK615双重抑制极光激酶A和B的表达。细胞周期分析显示，MK615增加了G2/M期的细胞数量。
结论
MK615通过双重抑制极光激酶A和B对人胰腺癌细胞发挥体外抗肿瘤作用。
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