新型化疗药物对视网膜母细胞瘤的体外药效实验
发布时间：2018-08-15 12:46
【摘要】： 一、目的： 1、研究肿瘤干细胞在视网膜母细胞瘤化疗耐药中的作用； 2、开发更有效的新型化疗药物并探索更科学的化疗方案 二、方法： 选用Y79细胞株及本课题组前期工作中自行建立的、具有肿瘤干细胞样特性的细胞株FD-RB作为研究的对象。用CCK-8的方法检测新型化疗药物拓扑替康、DG-2在不同浓度下对Y79细胞和FD-RB细胞的抑制作用,并与Rb传统化疗药物卡铂及长春新碱的体外作用做对照,用t检验的方法比较两株细胞在各种药物不同浓度下的存活率差异,同时比较新型化疗药物与传统化疗药物的半数抑制浓度(IC50),筛选出体外杀伤作用最强的化疗药物；将不同浓度的DG-2与拓扑替康、卡铂进行两两组合,检测联合用药下Y79和FD-RB的细胞存活率,用多重线性回归分析联合用药与单药使用的效用差异,并分析药物间的相互作用。 三、结果 FD-RB细胞的体外耐药性低于Y79细胞,两者的差异具有统计学意义(P0.05)；在四种检测药物中,拓扑替康的体外细胞杀伤作用仅次于长春新碱,它对Y79细胞的IC50约为6.52umol/L,对FD-RB细胞的IC50约为0.026umol/L; DG-2在有氧状态下也能有效杀伤两株细胞；拓扑替康与DG-2联合应用时可能会相互削弱的彼此的效用；卡铂和DG-2的体外联合用药未发现交互作用,两者的联合效应只是两者单独效应的叠加。 四、结论 从本研究的数据来看,肿瘤干细胞不一定是导致肿瘤耐药、化疗失败的唯一因素,其自身的耐药性也受多方面的影响。拓扑替康在体外对Y79及FD-RB细胞均有良好的杀伤作用,对于治疗复发转移的Rb具有潜在的临床应用价值；DG-2在正常氧供状态下也可抑制Y79及FD-RB细胞的生长,结合其降低缺氧相关的化疗耐药作用,DG-2在Rb中的治疗前景令人期待。拓扑替康与DG-2联合应用体内疗效有待进一步实验证实。
[Abstract]:Objective: 1. To study the role of tumor stem cells in chemotherapeutic resistance of retinoblastoma. (2) to develop more effective new chemotherapeutic drugs and to explore more scientific chemotherapeutic schemes. Methods: Y79 cell line and FD-RB cell line with tumor-like characteristics were selected as the research object. The inhibitory effects of topotecan DG-2 on Y79 cells and FD-RB cells at different concentrations were detected by CCK-8, and compared with those of carboplatin and vincristine, the traditional chemotherapeutic agents of RB in vitro. T test method was used to compare the survival rate of the two cell lines at different concentrations of various drugs, and to compare the half inhibitory concentration (IC50) between new and traditional chemotherapeutic drugs, and to screen out the most effective chemotherapeutic drugs in vitro. Different concentrations of DG-2 were combined with topotecan and carboplatin to detect the cell survival rate of Y79 and FD-RB. The effects of combination and single drug use were analyzed by multiple linear regression analysis. Results the drug resistance of FD-RB cells was lower than that of Y79 cells in vitro, and the difference was statistically significant (P0.05). The IC50 of Y79 cells was about 6.52 umolr / L, the IC50 of FD-RB cells was about 0.026 umol/ L, DG-2 could also kill two cell lines in aerobic state, topotecan and DG-2 might weaken each other. No interaction was found in the combination of carboplatin and DG-2 in vitro, but the combined effect was only the superposition of the two alone effects. Conclusion: according to the data of this study, tumor stem cells are not necessarily the only factor leading to drug resistance and chemotherapy failure, and their own drug resistance is also affected by many aspects. Topotecan has a good killing effect on Y79 and FD-RB cells in vitro, and has potential clinical application value for the treatment of recurrent and metastatic RB. DG-2 can also inhibit the growth of Y79 and FD-RB cells under normal oxygen supply. The therapeutic prospect of DG-2 in RB combined with its role in reducing chemoresistance associated with anoxia is promising. The in vivo efficacy of topotecan combined with DG-2 needs further experimental confirmation.
【学位授予单位】：复旦大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R739.7
本文编号：2184244
[Abstract]:Objective: 1. To study the role of tumor stem cells in chemotherapeutic resistance of retinoblastoma. (2) to develop more effective new chemotherapeutic drugs and to explore more scientific chemotherapeutic schemes. Methods: Y79 cell line and FD-RB cell line with tumor-like characteristics were selected as the research object. The inhibitory effects of topotecan DG-2 on Y79 cells and FD-RB cells at different concentrations were detected by CCK-8, and compared with those of carboplatin and vincristine, the traditional chemotherapeutic agents of RB in vitro. T test method was used to compare the survival rate of the two cell lines at different concentrations of various drugs, and to compare the half inhibitory concentration (IC50) between new and traditional chemotherapeutic drugs, and to screen out the most effective chemotherapeutic drugs in vitro. Different concentrations of DG-2 were combined with topotecan and carboplatin to detect the cell survival rate of Y79 and FD-RB. The effects of combination and single drug use were analyzed by multiple linear regression analysis. Results the drug resistance of FD-RB cells was lower than that of Y79 cells in vitro, and the difference was statistically significant (P0.05). The IC50 of Y79 cells was about 6.52 umolr / L, the IC50 of FD-RB cells was about 0.026 umol/ L, DG-2 could also kill two cell lines in aerobic state, topotecan and DG-2 might weaken each other. No interaction was found in the combination of carboplatin and DG-2 in vitro, but the combined effect was only the superposition of the two alone effects. Conclusion: according to the data of this study, tumor stem cells are not necessarily the only factor leading to drug resistance and chemotherapy failure, and their own drug resistance is also affected by many aspects. Topotecan has a good killing effect on Y79 and FD-RB cells in vitro, and has potential clinical application value for the treatment of recurrent and metastatic RB. DG-2 can also inhibit the growth of Y79 and FD-RB cells under normal oxygen supply. The therapeutic prospect of DG-2 in RB combined with its role in reducing chemoresistance associated with anoxia is promising. The in vivo efficacy of topotecan combined with DG-2 needs further experimental confirmation.
【学位授予单位】：复旦大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R739.7
【参考文献】
相关期刊论文 前2条
1 杨纯正;肿瘤耐药研究的若干问题[J];中华医学杂志;2001年24期
2 徐和平，祝和成，，王成业，顾焕华，刘双珍，许雪亮;视网膜母细胞瘤细胞系HXO－Rb_（44）化疗敏感性及多药耐药性研究[J];中国实用眼科杂志;1996年09期
本文编号：2184244
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