摘要
目的探讨银杏叶提取物(ginkgo biloba extract,EGb761)对顺铂诱导的胃癌细胞SGC-7901及胃癌耐药细胞SGC-7901/CDDP增殖和凋亡的影响及其对胃癌细胞化疗耐药的影响及其机制。方法采用EGb761、顺铂单用及EGb761与顺铂联合应用处理人胃癌细胞株SGC-7901及耐药细胞SGC-7901/CDDP,采用四甲基偶氮唑蓝(methyl thiazolyl tetrazolium,MTT)法检测两种细胞的增殖活性,流式细胞仪检测细胞凋亡,实时荧光定量PCR法、Western blot法检测两种细胞中NIBP、NF-κB P65 mR NA和蛋白的表达。结果顺铂和EGb761均对两种胃癌细胞的增殖具有抑制作用,呈剂量依赖性,但SGC-7901/CDDP细胞对顺铂的敏感性较SGC-7901/CDDP差。EGb761与顺铂联合应用可明显增强SGC-7901及SGC-7901/CDDP细胞株对顺铂的敏感性并促进细胞的凋亡。SGC-7901/CDDP细胞中NIBP和NF-κB p65的mR NA及蛋白相对表达水平均高于SGC-7901细胞(P<0.05),EGb761能明显抑制由顺铂诱导的NIBP和NF-κB p65的表达(P<0.05)。结论 EGb761具有显著的化疗增敏效果,并能逆转胃癌细胞耐药,增强顺铂对胃癌细胞生长的抑制作用并促进细胞凋亡。其逆转抗肿瘤细胞耐药和化疗增敏的作用机制可能是通过抑制NF-κB通路的活性,减少NIBP和NF-κB p65的表达而实现。
Objective To investigate the effect of ginkgo biloba extract（EGb761）on cisplatin-induced proliferation and apoptosis of gastric cancer cells（SGC-7901 and SGC-7901/CDDP）,and to observe its effect and mechanism on gastric cancer cells resistance to chemotherapy.Methods SGC-7901 and SGC-7901/CDDP cells were treated with EGb761,cisplatin or EGb761 combined with cisplatin.Cell proliferation activity was measured by methyl thiazolyl tetrazolium（MTT） assay,and apoptosis was measured by flow cytometry.The m RNA expression of NIK and IKKβbinding protein（NIBP） and nuclear factor-kappa B（NF-κB） p65 was detected by real-time PCR,and their protein expression was analyzed by Western blot.Results Monotherapy with EGb761 or cisplatin significantly inhibited the proliferation of SGC-790 l and SGC-7901/CDDP cells in a dose-dependent manner,but SGC-7901/CDDP cells were less sensitivity to cisplatin.EGb761 combined with cisplatin showed significant effect on enhancing the sensitivity of SGC-7901 and SGC-7901/CDDP to cisplatin,and promoted the apoptosis of the cells.NIBP and NF-κB p65 m RNA and protein expression levels in SGC-7901/CDDP cells were relatively higher than those in SGC-7901 cells（P〈0.05）,and EGb761 significantly inhibited cisplatin-induced NIBP and NF-κB p65 expression（P〈0.05）.Conclusion EGb761 has significant chemotherapy-sensitizing effect,reverses the drug resistance of gastric cancer cells,enhances the inhibitory effect of cisplatin on gastric cancer cells growth,and promotes apoptosis.Its anti-drug-resistance and chemotherapy-sensitizing mechanism may be achieved by inhibiting the activity of NF-κB pathway,reducing the expression of NF-κB p65 and NIBP.
出处
《中药新药与临床药理》
CAS
CSCD
北大核心
2016年第6期768-774,共7页
Traditional Chinese Drug Research and Clinical Pharmacology
基金
国家自然科学基金资助项目(81460380)
广西医疗卫生适宜技术研究与开发资金资助项目(S201415-01)
广西自然科学基金资助项目(2011GXNSFA018182)
广西卫生厅基金资助项目(GZKZ10-107)
