大黄酚对结肠癌的抗肿瘤作用

doi:10.6040/j.issn.1671-7554.0.2018.1332

摘要/Abstract

摘要： 目的探讨大黄酚对结肠癌的抗癌作用。方法以CCK-8测定细胞活性,Tunel法和Annexin V-FITC/PI法检测细胞凋亡,Western blotting测定蛋白表达;建立移植瘤小鼠模型,观察小鼠体质量以及肿瘤体积变化。结果细胞实验中,发现2、5 μmol/L浓度的大黄酚可以使Tunel阳性率由(1.3±0.3)%分别增加到(8.5±1.3)%和(18.6±2.9)%(n=3,F=66.7,P<0.01),Annexin V-FITC/PI凋亡率由(4.2±0.3)%增至(9.6±1.3)%和(19.2±2.6)%(n=3,F=60.83,P<0.01); HCT116结肠癌细胞48 h活性下降为(77.2±6.5)%和(61.3±7.2)%(n=3,F=5.97,P<0.01);Caspase-9和Caspase-3特异性抑制剂使大黄酚诱导的细胞凋亡率由(19.2±2.6)%下降为(6.0±0.4)%和(7.2±0.6)% (n=3,F=56.37,P<0.01);日剂量给予10 mg/kg和20 mg/kg大黄酚能够抑制小鼠移植瘤体积(n=6,F=9.48~13.79,P<0.01),并促进移植瘤凋亡,凋亡率由(1.8±0.5)%上升至(9.7±1.6)% 和(16.3±3.0)%(n=3,F=40.16,P<0.01)。结论大黄酚在结肠癌临床治疗中具有潜在价值。

关键词: 大黄酚, 结肠癌, 凋亡, 线粒体途径, 小鼠

Abstract: Objective To explore the anticancer effect of chrysophanol on colorectal cancer. Methods The viability of colorectal cancer cells was detected with CCK-8. The apoptosis was determined with Tunel and Annexin V-FITC/PI staining. The protein expression was assessed with Western blotting. The tumor xenograft mice models were established and the body weight and tumor column were observed. Results The 2 μmol/L and 5 μmol/L chrysophanol increased the positive rate of Tunel from(1.3±0.3)% to(8.5±1.3)% and(18.6±2.9)% (n=3, F=66.7, P<0.01), respectively; increased the apoptosis rate of Annexin V-FITC/PI from(4.2±0.3)% to(9.6±1.3)% and(19.2±2.6)% (n=3, F=60.83, P<0.01), respectively; decreased the 48 h activity of HCT116 colon cancer cells to(77.2±6.5)% and(61.3±7.2)% (n=3, F=5.97, P<0.01), respectively. Caspase-9 and Caspase-3 specific inhibitors could reduce the apoptosis rate induced by chrysophanol from(19.2±2.6)% to(6.0±0.4)% and(7.2±0.6)% (n=3, F=56.37, P<0.01), respectively. Daily dosage of 10 mg/kg and 20 mg/kg chrysophanol could inhibit the volume of transplanted tumor in mice (n=6, F=9.48-13.79, P<0.01), and increase the apoptosis rate from(1.8±0.5)% to(9.7±1.6)% and(16.3±3.0)% (n=3, F=40.16, P<0.01), respectively. Conclusion Chrysophanol can be a potential candidate drug for the treatment of colorectal cancer.

Key words: Chrysophanol, Colorectal cancer, Apoptosis, Mitochondrial pathway, Mouse

中图分类号:

R735.3

万秀霞,孙秀萍,佟晶洁. 大黄酚对结肠癌的抗肿瘤作用[J]. 山东大学学报 (医学版), 2019, 57(5): 74-79.

WAN Xiuxia, SUN Xiuping, TONG Jingjie. Anticancer effect of chrysophanol on colorectal cancer[J]. Journal of Shandong University (Health Sciences), 2019, 57(5): 74-79.

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