本文選題：膀胱癌 + 吉西他濱��； 參考：《蚌埠醫(yī)學(xué)院》2014年碩士論文

【摘要】：研究背景：膀胱癌是泌尿系統(tǒng)中最常見的腫瘤，近年來膀胱癌的發(fā)病率有逐漸升高的趨勢，已經(jīng)成為嚴(yán)重威脅人類健康的常見疾��；隨著醫(yī)療水平的提高，化療藥物的出現(xiàn)明顯降底了膀胱癌術(shù)后的復(fù)發(fā)率。吉西他濱是目前臨床一線的化療藥物，通過作用于DNA合成期阻止其進(jìn)展來發(fā)揮抗腫瘤的效應(yīng)，在膀胱腫瘤的治療中，其療效已經(jīng)得到大量臨床試驗的驗證。最近有研究表明吉西他濱能通過微小RNA (miRNA)發(fā)揮其抗腫瘤作用；miRNA是一類非編碼小分子RNA，通過與靶基因mRNA的不完全配對從而抑制其翻譯或直接將其降解；作為重要的基因調(diào)控因子發(fā)揮著癌基因或抑癌基因的作用。MiRNA與腫瘤發(fā)生發(fā)展的關(guān)系成為近年來的研究熱點。雖然在治療膀胱癌上有一定的療效，但是藥物的作用靶點以及轉(zhuǎn)錄后水平的調(diào)節(jié)機制還尚不清楚；本研究采用基因芯片技術(shù)，通過檢測吉西他濱干預(yù)膀胱腫瘤T-24細(xì)胞后miRNA表達(dá)譜的差異性來分析其可能抑制膀胱腫瘤細(xì)胞生長的機制。 目的：探究吉西他濱對膀胱腫瘤T24細(xì)胞miRNA表達(dá)譜的影響。 方法：培養(yǎng)膀胱腫瘤T-24細(xì)胞株，待其傳代生長后用MTT法檢測細(xì)胞增殖情況并計算吉西他濱的半數(shù)抑制濃度（即IC50);用此濃度刺激T-24細(xì)胞24h后，利用miRNA芯片技術(shù)檢測用藥前后T-24細(xì)胞miRNA的表達(dá)，對其表達(dá)譜進(jìn)行差異性分析，并篩選出差異表達(dá)的miRNA分子。 結(jié)果：1.T-24細(xì)胞的生長抑制率與吉西他濱之間存在一定的濃度依賴關(guān)系，測出其IC50為1.403ug/ml。 2.用IC50刺激T24細(xì)胞24h后，利用miRNA芯片技術(shù)檢測加藥刺激后的樣本與未加藥的樣本比較。共測得有152個與吉西他濱加藥刺激相關(guān)的miRNA差異表達(dá)，其中與未刺激的樣本比較明顯上調(diào)的有7個，包括miR-200c-5p,miR-3689b-3p/miR-3689c，miR-2355-5p，miR-195-3p，miR-23b-5p，miR-4648禾口miR-3929；明顯下調(diào)的有11個，包括miR-802，miR-1252-5p，miR-5009-3p，miR-5003-5p，miR-874-3p，miR-216a-5p? miR-4736，miR-548aa/miR-548ap-3/miR-548t-3p?miR-548h-3p/miR-548z，miR-3688-5p，，miR-2681-3p。 結(jié)論：1.吉西他濱與膀胱腫瘤T-24細(xì)胞的增殖呈濃度依賴關(guān)系；并且吉西他濱的干預(yù)能夠使T-24細(xì)胞的miRNA表達(dá)譜發(fā)生改變 2.吉西他濱對miRNA的表達(dá)調(diào)控可能是其抗膀胱腫瘤T-24細(xì)胞的重要途徑。
[Abstract]:Background: bladder cancer is the most common tumor in the urinary system. In recent years, the incidence of bladder cancer has gradually increased, which has become a serious threat to human health. The appearance of chemotherapeutic drugs significantly reduced the recurrence rate of bladder cancer after operation. Gemcitabine is one of the first-line chemotherapeutic drugs in clinic at present. It has been proved by a large number of clinical trials that gemcitabine can prevent the progress of DNA in the synthetic phase to play an anti-tumor effect. Recent studies have shown that gemcitabine can play its anti-tumor effect through small RNA miRNAs. It is a kind of non-coding small molecule RNAs, which inhibits its translation or directly degrades by incomplete pairing with the target gene mRNA. As an important gene regulator, the role of oncogene or tumor suppressor gene. MiRNA has become a hot topic in recent years. Although there are some therapeutic effects in the treatment of bladder cancer, the target of the drug and the regulation mechanism of posttranscriptional level are still unclear. By detecting the difference of miRNA expression profile after gemcitabine intervention in bladder tumor T-24 cells, the mechanism of inhibition of bladder tumor cell growth was analyzed. Objective: to investigate the effect of gemcitabine on miRNA expression profile of bladder tumor T 24 cells. Methods: the bladder tumor T-24 cell line was cultured. The proliferation of T-24 cells was detected by MTT method and the half inhibitory concentration (IC50) of gemcitabine was calculated after 24 h stimulation of T-24 cells. The expression of miRNA in T-24 cells before and after treatment was detected by miRNA chip technique. The differential expression profiles were analyzed and the differential expression miRNA molecules were screened out. Results there was a concentration-dependent relationship between the growth inhibition rate and gemcitabine, and the IC50 was 1.403U / ml. 2. After T24 cells were stimulated with IC50 for 24 hours, miRNA microarray technique was used to detect the comparison between the samples stimulated by IC50 and those without. 鍏辨祴寰楁湁152涓笌鍚夎タ浠栨花鍔犺嵂鍒烘縺鐩稿叧鐨刴iRNA宸紓琛ㄨ揪,鍏朵腑涓庢湭鍒烘縺鐨勬牱鏈瘮杈冩槑鏄句笂璋冪殑鏈

本文編號：1891309