β-elemene通过调节耐药特异性miRNA逆转乳腺癌细胞耐药性的机制研究  

Research of the Mechanism of β-elemene Reverse Drug Resistance in Breast Cancer Cells by Regulating Specific MiRNA

作　　者：邓恒[1] 马春耕[1] 张珺[2] HENG Deng;CHUNGENG Ma;JUN Zhang(The Second Affiliated Hospital of Anhui University of Chinese Medicine,Anhui Hefei 230001,China;Anhui University of Chinese Medicine,Anhui Hefei 230038,China)

机构地区：[1]安徽中医药大学第二附属医院肛肠科,安徽合肥230001 [2]安徽中医药大学中医基础教研室,安徽合肥230001

出　　处：《中医药临床杂志》2019年第5期901-906,共6页Clinical Journal of Traditional Chinese Medicine

基　　金：安徽省自然科学基金项目--基于微泡介导的微小RNA信息传递机制研究B-elemene抗乳腺癌耐药(NO.1808085MH302)

摘　　要：目的:探讨β-榄香烯逆转乳腺癌细胞耐药性的机制,明确其抗肿瘤作用。方法:通过向MCF-7细胞株培养基内逐渐增加临床上最常用于乳腺癌化学治疗的药物多西紫杉醇(Doc)或阿霉素(Adr),逐渐提高培养基中药物浓度的方法成功地构建出亲本细胞株MCF-7中耐药亚型,选择乳腺癌阿霉素耐药细胞(MCF-7/Adr)和乳腺癌多西紫杉醇(MCF-7/Doc)耐药细胞株,采用MTT-cytotoxic、miRNA微阵列、实时定量PCR、双荧光素酶活性测定等方法,研究β-elemene对乳腺癌耐药细胞生存率、耐药特异性miRNA29a、miRNA452、miRNA34a及miRNA222表达的影响。结果:β-elemene明显降低耐药乳腺癌细胞株细胞生存率和增殖率,β-elemene显著调节MCF-7/Adr和MCF-7/Doc细胞内miRNAs的表达水平,其中6个miRNAs上调,12个miRNAs下调显著。结论:β-elemene是一种从植物中提取的天然抗肿瘤中药成分,可以逆转乳腺癌细胞的耐药性。证实了中药β-elemene可以通过调控耐药相关miRNA表达的机制抗乳腺癌耐药细胞的耐药性。Objective: To explore the mechanism of the reversal of drug resistance in breast cancer cells and its antitumor effect. Methods: Through the MCF-7 cell lines within the medium increased the most commonly used clinical breast cancer chemotherapy drug Docetaxel(Doc) and Adriamycin(Adr), and gradually improve the drug concentrations in the culture medium method successfully build a parent cell line MCF-7 resistant sub-types, choose Adriamycin resistance of breast cancer cells(MCF-7/Adr) and breast cancer Docetaxel(MCF-7/Doc) drug resistant cell lines, the determined by MTT-cytotoxic, microRNAs microarray and real-time quantitative PCR, double luciferase activity determination methods, such as to investigate the effects of β-elemene on survival rate of breast cancer drug-resistant cells, drug-resistant specific miRNA-29 a, miRNA-452, miRNA-34 a and miRNA-222 expression. Results: The survival rate and proliferation rate of drug-resistant breast cancer cell lines were significantly reduced by β-elemene,while the expression level of miRNAs in McF-7/Adr and McF-7/Doc cells was significantly regulated by β-elemene,6 miRNAs of which were up-regulated and 12 of which were significantly down-regulated. Conclusion:β-elemene is a kind of natural anti-tumor Chinese medicine component extracted from plants, which can reverse the drug resistance of breast cancer cells. It was confirmed that β-elemene of traditional Chinese medicine could regulate the resistanceof breast cancer resistant cells by regulating the expression of drug-resist ant miRNA.

关 键 词：Β-ELEMENE 耐药性 乳腺癌 机制 

分 类 号：R73-3[医药卫生—肿瘤]