柯里拉京对顺铂抗卵巢癌Hey和SKOV3细胞的增敏作用
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摘要
探讨柯里拉京(corilagin)与羟基喜树碱(HCPT)、顺铂(cDDP)单独及联合用药,体外抗卵巢癌细胞Hey,SKOV3的活性及与cDDP联用机制的初步研究.利用四唑盐(MTT)比色法检测柯里拉京,HCPT,cDDP在不同质量浓度下,单独及联合用药对卵巢癌细胞的增殖抑制率,并根据金氏公式计算其协同指数(Q),进而评价两药联用的增敏效果.通过形态学观察吖啶橙(AO)/溴化乙啶(EB)和Hoechst 33258染色及线粒体膜电位变化,探究其诱导机制.结果表明:柯里拉京对卵巢细胞Hey,SKOV3的半抑制浓度(IC_(50)值)分别为19.20,17.17μmol·L~(-1);柯里拉京与cDDP联合作用对于SKOV3,Hey两种细胞均有协同作用,与HCPT联用只对SKOV3细胞有协同作用,对Hey细胞仅是相加效应;联合用药组对卵巢癌细胞的抑制效果显著高于单独用药组;柯里拉京与cDDP联合用药对卵巢癌细胞的杀伤效果可能是通过诱导细胞凋亡实现的.
The activity against ovarian cancer cells(Hey,SKOV3)was investigated in vitro using corilagin,hydroxy camptothecine(HCPT),and cisplatin(cDDP)alone or in combination,and the combination mechanism of corilagin with cDDP was preliminarily studied.The inhibitory rate of corilagin,HCPT and cDDP alone or in combination with different concentrations on ovarian cancer cells was also determined by methyl thiazolyl tetrazolium(MTT)method.And the synergistic index(Q)which assesses the sensitization effect of colilagin for HCPT and cDDP was calculated according to Kim′s formula.In addition,morphological observation and apoptosis staining including acridine orange(AO)/ethidium bromide(EB)and Hoechst 33258 and mitochondrial membrane potential staining were used to explore its potential induction mechanism.The results show that the half maximal inhibitory concentration(IC_(50) values)of corilagin on the ovarian cells Hey and SKOV3 were 19.20 and 17.17μmol·L~(-1),respectively.The combination of corilagin and cDDP had synergistic effects on both SKOV3 and Hey cells,while the combination of colilagin and HCPT only had synergistic effect on SKOV3 and additive effect on Hey.The inhibitory effect of combination therapy group on ovarian cancer cells was significantly higher than that of the control group.Moreover,the killing effect of corilagin in combination with cisplatin on ovarian cancer cells may be realized through the induction of cell apoptosis.
The activity against ovarian cancer cells(Hey,SKOV3)was investigated in vitro using corilagin,hydroxy camptothecine(HCPT),and cisplatin(cDDP)alone or in combination,and the combination mechanism of corilagin with cDDP was preliminarily studied.The inhibitory rate of corilagin,HCPT and cDDP alone or in combination with different concentrations on ovarian cancer cells was also determined by methyl thiazolyl tetrazolium(MTT)method.And the synergistic index(Q)which assesses the sensitization effect of colilagin for HCPT and cDDP was calculated according to Kim′s formula.In addition,morphological observation and apoptosis staining including acridine orange(AO)/ethidium bromide(EB)and Hoechst 33258 and mitochondrial membrane potential staining were used to explore its potential induction mechanism.The results show that the half maximal inhibitory concentration(IC_(50) values)of corilagin on the ovarian cells Hey and SKOV3 were 19.20 and 17.17μmol·L~(-1),respectively.The combination of corilagin and cDDP had synergistic effects on both SKOV3 and Hey cells,while the combination of colilagin and HCPT only had synergistic effect on SKOV3 and additive effect on Hey.The inhibitory effect of combination therapy group on ovarian cancer cells was significantly higher than that of the control group.Moreover,the killing effect of corilagin in combination with cisplatin on ovarian cancer cells may be realized through the induction of cell apoptosis.
引文
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[3] GUO Yuanjin,ZHAO Lei,LI Xiaofeng,et al.Effect of corilagin on anti-inflammation in HSV-1encephalitis and HSV-1infected microglias[J].European Journal of Pharmacology,2010,635(1/2/3):79-86.DOI:10.1016/j.ejphar.2010.02.049.
[4] DENG Yuan,LI Xudan,LI Xuan,et al.Corilagin induces the apoptosis of hepatocellular carcinoma cells through the mitochondrial apoptotic and death receptor pathways[J].Oncology Reports,2018,39(6):2545-2552.DOI:10.3892/or.2018.6396.
[5] SASIDHARAN I,SUNDARESAN A,NISHA V M,et al.Inhibitory effect of Terminalia chebula Retz.fruit extracts on digestive enzyme related to diabetes and oxidative stress[J].Journal of Enzyme Inhibition and Medicinal Chemistry,2012,27(4):578-586.DOI:10.3109/14756366.2011.603130.
[6]刘朝阳,王徳昌,陈玉武,等.柯里拉京抗肿瘤作用的研究[J].肿瘤防治研究,2002,29(5):356-358.DOI:10.3971/j.issn.1000-8578.2002.05.003.
[7] HONMA A,KOYAMA T,YAZAWA K.Antihyperglycemic effects of Japanese maple Acer amoenum,leaf extract and its constituent corilagin[J].Journal of Wood Science,2010,56(6):507-512.DOI:10.1007/s10086-010-1130-5.
[8] MING Yanlin,ZHENG Zhizhong,CHEN Lianghua,et al.Corilagin inhibits hepatocellular carcinoma cell proliferation by inducing G2/M phase arrest[J].Cell Biology International,2013,37(10):1046-1054.DOI:10.1002/cbin.10132.
[9] JIA Luoqi,JIN Hongyan,ZHOU Jiayi,et al.A potential anti-tumor herb medicine,corilagin,inhibits ovarian cancer cell growth by blockage of TGF-β/AKT/ERK signaling pathways[J].BMC Complementary and Alternative Medicine,2013,13(1):33-44.DOI:10.1186/1472-6882-13-33.
[10]康健,张岩岩,陈冬,等.柯里拉京对人喉癌Hep-2细胞生长的研究[J].中药药理与临床,2012,28(6):24-27.DOI:10.13412/j.cnki.zyyl.2012.06.010.
[11] GU Yue,XIAO Linfeng,MING Yanlin,et al.Corilagin suppresses cholangiocarcinoma progression through Notch signaling pathway in vitro and in vivo[J].International Journal of Oncology,2016,48(5):1868-1876.DOI:10.3892/ijo.2016.3413.
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[13]童宇星.Corilagin的提取制备及其抗肿瘤作用机制研究[D].厦门:华侨大学,2012.
[14]徐韬,许瑞安.中药及其有效成分抗肿瘤作用机制研究进展[J].华侨大学学报(自然科学版),2009,30(4):359-365.DOI:10.11830/ISSN.1000-5013.2009.04.0359.
[15]陈一燕,陈崇宏.柯里拉京药理活性研究进展[J].中国现代应用药学,2010,27(5):390-394.DOI:10.13748/j.cnki.issn1007-7693.2010.05.005.
[16] GAMBARI R,HAU D K,WONG W Y,et al.Sensitization of Hep3Bhepatoma cells to cisplatin and doxorubicin by corilagin[J].Phytotherapy Research,2014,28(5):781-783.DOI:10.1002/ptr.5049.