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血根碱对紫杉醇耐药卵巢癌A2780/taxol细胞生长及化疗敏感性影响的研究
赵洪波;王妍妍;冷天艳;杨丽华;
0
(昆明医科大学分子临床医学研究院; 昆明医科大学第二附属医院)
摘要:
目的:探讨血根碱对紫杉醇耐药卵巢癌A2780/taxol细胞生长及化疗敏感性的影响和机制。方法:培养A2780/taxol细胞,分为对照组、血根碱组、紫杉醇组、血根碱+紫杉醇组,对照组加0.9%氯化钠液,血根碱组加2.0μmol/L血根碱,紫杉醇组加2μg/ml紫杉醇,血根碱+紫杉醇组同时加2.0μmol/L血根碱及2μg/ml紫杉醇。应用MTT法、流式细胞仪和Western blot法检测血根碱对A2780/taxol细胞增殖、凋亡、克隆形成及Bax、β-tubulinⅢ蛋白表达的影响。结果:与对照组相比,血根碱组、紫杉醇组及血根碱+紫杉醇组均能显著抑制A2780/taxol细胞增殖,血根碱+紫杉醇组抑制率最高(P<0.05);紫杉醇组、血根碱组及血根碱+紫杉醇组细胞克隆形成率[(35.67±7.37)%、(27.67±2.52)%和(8.87±3.38)%]明显降低,血根碱+紫杉醇组降低最为明显(P<0.05);紫杉醇组、血根碱组及血根碱+紫杉醇组细胞凋亡率[(18.01±7.13)%、(57.03±12.91)%和(81.68±11.23)%]明显增加,血根碱+紫杉醇组细胞凋亡率最高(P<0.05);紫杉醇组、血根碱组、血根碱+紫杉醇组Bax蛋白表达显著上调、β-tubulinⅢ蛋白表达显著降低,血根碱+紫杉醇组表达量变化最大(P<0.05)。结论:血根碱可下调β-tubulinⅢ表达,诱导肿瘤细胞凋亡,增强紫杉醇对耐药卵巢癌细胞的生长抑制作用,从而促进其对紫杉醇药物的敏感性。
关键词:  血根碱  紫杉醇  耐药  卵巢癌  化疗敏感性
DOI:
基金项目:云南省卫生和计划生育委员会医学学科带头人培养项目(编号:D-201633);国家自然科学基金地区项目(编号:81360336);云南省教育厅科学研究基金项目重点项目(编号:2015Z074);云南省科技厅—昆明医科大学应用基础研究联合专项资金面上项目[编号:2017FE467(-062)]
The Effect of Growth and Chemotherapy Sensitivity on Ovarian Cancer Cells A2780/taxol by Sanguinarine
ZHAO Hongbo;WANG Yanyan;LENG Tianyan
(The Molecule Clinical Research Institute of Kunming Medical University;The Second Affiliated Hospital of Kunming Medical University)
Abstract:
Objective: Investigate the role and mechanism of sanguinarine to reverse paclitaxel drug resistance to paclitaxel resistant ovarian cancer cell A2780/taxol by sanguinarine.Methods: Paclitaxel resistant ovarian cancer A2780/taxol cells were divided into control group,sanguinarine group,paclitaxel and paclitaxel combined sanguinarine group.The cells in control group were treated with NS; The cells in sanguinarine group were treated with2. 0 μmol/L sanguinarine; The cells in paclitaxel group were treated with paclitaxel; the cells in the paclitaxel combined sanguinarine group were treated with 2. 0 μmol/L paclitaxel and 2 μg/ml sanguinarine at the concentration of at the same time.The proliferation,apoptosis and the expression of Bax,β-tubulinⅢwere determined by MTT method,the clone formation,Flow cytometry and Western blot.Results: Compared with control group,the proliferation of cells in the sanguinarine,paclitaxel and paclitaxel combined sanguinarine group were significantly inhibited( P<0. 05).The clone formation of cells were[( 35. 67±7. 37) %、( 27. 67±2. 52) % and( 8. 87±3. 38) %]in the sanguinarine,paclitaxel and paclitaxel combined sanguinarine group respectively,which were significantly decreased.The apoptosis rate were[( 18. 01±7. 13) %,( 57. 03±12. 91) % and( 81. 68±11. 23) %]in the sanguinarine,paclitaxel and paclitaxel combined sanguinarine group respectively,which were increased significantly.The expression of Bax were up-regulated while the expression of β-tubulinⅢ were down regulated. The proliferation,clone formation,apoptosis rate,the expressions of Bax and β-tubulin Ⅲ were significantly different among them,which were most obvious in paclitaxel combined sanguinarine group( P < 0. 05). Conclusions: Sanguinarine can down-regulate the expression of tubulinⅢ,induce the apotosis and enhance the inhibition effect of A2780/taxol cells then promote paclitaxel drug sensitivity
Key words:  Sanguinarine  Paclitaxel  Drugresistance  Ovariancancer  Chemosensitivity

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