【摘要】： 一、目的： 1、研究腫瘤干細(xì)胞在視網(wǎng)膜母細(xì)胞瘤化療耐藥中的作用； 2、開發(fā)更有效的新型化療藥物并探索更科學(xué)的化療方案 二、方法： 選用Y79細(xì)胞株及本課題組前期工作中自行建立的、具有腫瘤干細(xì)胞樣特性的細(xì)胞株FD-RB作為研究的對象。用CCK-8的方法檢測新型化療藥物拓?fù)涮婵怠G-2在不同濃度下對Y79細(xì)胞和FD-RB細(xì)胞的抑制作用,并與Rb傳統(tǒng)化療藥物卡鉑及長春新堿的體外作用做對照,用t檢驗(yàn)的方法比較兩株細(xì)胞在各種藥物不同濃度下的存活率差異,同時(shí)比較新型化療藥物與傳統(tǒng)化療藥物的半數(shù)抑制濃度(IC50),篩選出體外殺傷作用最強(qiáng)的化療藥物；將不同濃度的DG-2與拓?fù)涮婵怠⒖ㄣK進(jìn)行兩兩組合,檢測聯(lián)合用藥下Y79和FD-RB的細(xì)胞存活率,用多重線性回歸分析聯(lián)合用藥與單藥使用的效用差異,并分析藥物間的相互作用。 三、結(jié)果 FD-RB細(xì)胞的體外耐藥性低于Y79細(xì)胞,兩者的差異具有統(tǒng)計(jì)學(xué)意義(P0.05)；在四種檢測藥物中,拓?fù)涮婵档捏w外細(xì)胞殺傷作用僅次于長春新堿,它對Y79細(xì)胞的IC50約為6.52umol/L,對FD-RB細(xì)胞的IC50約為0.026umol/L; DG-2在有氧狀態(tài)下也能有效殺傷兩株細(xì)胞；拓?fù)涮婵蹬cDG-2聯(lián)合應(yīng)用時(shí)可能會(huì)相互削弱的彼此的效用；卡鉑和DG-2的體外聯(lián)合用藥未發(fā)現(xiàn)交互作用,兩者的聯(lián)合效應(yīng)只是兩者單獨(dú)效應(yīng)的疊加。 四、結(jié)論 從本研究的數(shù)據(jù)來看,腫瘤干細(xì)胞不一定是導(dǎo)致腫瘤耐藥、化療失敗的唯一因素,其自身的耐藥性也受多方面的影響。拓?fù)涮婵翟隗w外對Y79及FD-RB細(xì)胞均有良好的殺傷作用,對于治療復(fù)發(fā)轉(zhuǎn)移的Rb具有潛在的臨床應(yīng)用價(jià)值；DG-2在正常氧供狀態(tài)下也可抑制Y79及FD-RB細(xì)胞的生長,結(jié)合其降低缺氧相關(guān)的化療耐藥作用,DG-2在Rb中的治療前景令人期待。拓?fù)涮婵蹬cDG-2聯(lián)合應(yīng)用體內(nèi)療效有待進(jìn)一步實(shí)驗(yàn)證實(shí)。
[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.
【學(xué)位授予單位】：復(fù)旦大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2010
【分類號(hào)】：R739.7

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