本文選題：骨肉瘤 + 化療耐藥　； 參考：《臨床與實驗病理學(xué)雜志》2017年04期

【摘要】：目的探討FoxM1是否調(diào)控DNA修復(fù)基因Rad51參與順鉑(CDP)對骨肉瘤耐藥細(xì)胞化療抑制作用。方法采用逐步增加劑量間歇作用的方法誘導(dǎo)骨肉瘤耐藥細(xì)胞系并分別命名為MG-63/R和HOS-MNNG/R。qRT-PCR、Western blot法檢測耐藥細(xì)胞與親本細(xì)胞FoxM1和Rad51的mRNA及蛋白表達(dá);耐藥細(xì)胞中4μmol/L Thiostrepton處理后qRT-PCR、Western blot法檢測FoxM1和Rad51的mRNA及蛋白表達(dá)。細(xì)胞計數(shù)法檢測單獨或聯(lián)合運(yùn)用4μmol/L Thiostrepton和2μg/m L CDP對骨肉瘤耐藥細(xì)胞增殖率的影響。結(jié)果建立在2μg/mL CDP濃度中穩(wěn)定生長的耐藥細(xì)胞系MG-63/R和HOS-MNNG/R,耐藥指數(shù)分別為30.52和37.87(均重度耐藥)。FoxM1和Rad51的mRNA及蛋白水平在耐藥細(xì)胞中表達(dá)較親本細(xì)胞明顯增高;在耐藥細(xì)胞中聯(lián)合運(yùn)用4μmol/L Thiostrepton和2μg/mL CDP組較單獨應(yīng)用4μmol/L Thiostrepton組或2μg/mL CDP組細(xì)胞增殖率明顯降低;耐藥細(xì)胞4μmol/L Thiostrepton處理后FoxM1及Rad51的mRNA和蛋白表達(dá)均明顯降低。結(jié)論 FoxM1及Rad51高表達(dá)可能參與骨肉瘤細(xì)胞對CDP耐藥,FoxM1抑制劑Thiostrepton可能通過下調(diào)Rad51增強(qiáng)CDP對骨肉瘤耐藥細(xì)胞的抑制作用。
[Abstract]:Objective to investigate whether FoxM1 regulates the role of DNA repair gene Rad51 in the inhibition of chemotherapeutic effects of cisplatin on drug-resistant osteosarcoma cells. Methods the drug-resistant osteosarcoma cell lines were induced by increasing the dose intermittently and named as MG-63/R and HOS-MNNGR / R.qRT-PCRN Western blot method respectively to detect the expression of mRNA and protein in FoxM1 and Rad51 of resistant and parental cells. After 4 渭 mol/L Thiostrepton treatment, the expression of mRNA and protein in FoxM1 and Rad51 were detected by qRT-PCR- Western blot. The effect of 4 渭 mol/L Thiostrepton and 2 渭 g / mL CDP alone or in combination on the proliferation of drug-resistant osteosarcoma cells was detected by cell counting method. Results the drug resistant cell lines MG-63/R and HOS-MNNGR, which grew stably at 2 渭 g/mL CDP concentration, had a drug resistance index of 30.52 and 37.87, respectively. The mRNA and protein levels of both severe drug resistant cells, FoxM1 and Rad51 were significantly higher than those of their parent cells. The proliferation rate of the cells treated with 4 渭 mol/L Thiostrepton and 2 渭 g/mL CDP was significantly lower than that of the 4 渭 mol/L Thiostrepton or 2 渭 g/mL CDP groups, and the mRNA and protein expressions of FoxM1 and Rad51 were significantly decreased after 4 渭 mol/L Thiostrepton treatment. Conclusion the high expression of FoxM1 and Rad51 may be involved in the inhibition effect of CDP on CDP resistant osteosarcoma cells by down-regulation of Rad51.
【作者單位】： 安徽醫(yī)科大學(xué)基礎(chǔ)醫(yī)學(xué)院病理學(xué)教研室;安徽醫(yī)科大學(xué)第一附屬醫(yī)院骨科;
【基金】：國家自然科學(xué)青年基金(81102041) 安徽省自然科學(xué)基金(11040606Q17)
【分類號】：R738.1

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