本文選題：奧希替尼　切入點(diǎn)：地塞米松　出處：《錦州醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的本實(shí)驗(yàn)通過(guò)體外細(xì)胞培養(yǎng)和荷瘤小鼠實(shí)驗(yàn),觀察抗癌新藥奧希替尼聯(lián)合地塞米松對(duì)腫瘤的抑制效果,分析其聯(lián)合使用的優(yōu)勢(shì),為臨床聯(lián)合用藥及進(jìn)一步研究復(fù)方制劑的制備提供相應(yīng)的參考數(shù)據(jù)。方法以不同濃度的奧希替尼、地塞米松及兩者聯(lián)合用藥的方式分別作用于非小細(xì)胞肺癌細(xì)胞株H1975。在24、48、72h后,應(yīng)用四甲基偶氮唑藍(lán)(MTT)比色法檢測(cè)細(xì)胞增殖抑制情況;建立小鼠荷肺癌模型后,按照奧希替尼組、地塞米松組、聯(lián)合用藥組和對(duì)照組的分組模式連續(xù)測(cè)量小鼠腫瘤體積和小鼠體重,分別繪制腫瘤生長(zhǎng)曲線和小鼠體重變化曲線,觀察各藥物組的作用效果。同時(shí)利用免疫組化S-ABC法測(cè)定各組對(duì)與炎癥產(chǎn)生和腫瘤血管生成有關(guān)的HIF-1a及NF-κB的抑制情況,并將各組數(shù)據(jù)進(jìn)行比較。結(jié)果通過(guò)MTT實(shí)驗(yàn)測(cè)得單獨(dú)用藥組和聯(lián)合用藥組對(duì)H1975細(xì)胞的抑制率,經(jīng)SPSS數(shù)據(jù)分析,LSD數(shù)據(jù)比較發(fā)現(xiàn),地塞米松不同藥物濃度組在24h、48h以及72h的細(xì)胞抑制率均不存在顯著性差異(P≥0.05);奧希替尼不同藥物濃度組在24h、48h以及72h的細(xì)胞抑制率均存在顯著性差異(P≤0.05);聯(lián)合用藥組對(duì)比于奧希替尼單獨(dú)用藥組在24h、48h以及72h的細(xì)胞抑制率不存在顯著性差異(P≥0.05)。單獨(dú)使用地塞米松和奧希替尼,其腫瘤體積和小鼠體重變化速度顯著低于對(duì)照組,最優(yōu)組為聯(lián)合用藥組,其腫瘤生長(zhǎng)速度明顯放緩,小鼠體重得到明顯控制且與對(duì)照組和單獨(dú)使用藥物的試驗(yàn)組有顯著性差異(P≤0.05)。通過(guò)免疫組化S-ABC法測(cè)定各組對(duì)HIF-1a及NF-κB的抑制強(qiáng)度,發(fā)現(xiàn)各組HIF-1a、NF-κB表達(dá)情況均有顯著下降(P≤0.05)。聯(lián)合用藥組對(duì)HIF-1a、NF-κB表達(dá)抑制最強(qiáng),且與對(duì)照組和單獨(dú)使用藥物的試驗(yàn)組有顯著性差異(P≤0.05)。應(yīng)用常規(guī)組織學(xué)染色法在顯微鏡下觀察聯(lián)合用藥組處理后小鼠腫瘤塊組織結(jié)構(gòu),對(duì)比單獨(dú)使用奧希替尼組處理后小鼠腫瘤塊組織結(jié)構(gòu),可以發(fā)現(xiàn)聯(lián)合用藥處理后的腫瘤塊內(nèi)部腫瘤血管明顯減少,顏色發(fā)白。結(jié)論地塞米松對(duì)非小細(xì)胞肺癌細(xì)胞株H1975抑制效果不顯著。奧希替尼對(duì)非小細(xì)胞肺癌細(xì)胞株H1975具有很強(qiáng)的抑制作用。相對(duì)于單獨(dú)使用奧希替尼,聯(lián)合地塞米松用藥并沒(méi)有增加對(duì)H1975的抑制效果。但地塞米松可顯著降低HIF-1a、NF-κB的表達(dá),近而抑制炎癥和腫瘤血管的生成。相對(duì)于單獨(dú)用藥,聯(lián)合用藥可顯著提高對(duì)HIF-1a、NF-κB表達(dá)的抑制效果,聯(lián)合用藥后腫瘤結(jié)構(gòu)內(nèi)血管明顯減少,顏色發(fā)白。通過(guò)小鼠實(shí)驗(yàn)可以發(fā)現(xiàn),聯(lián)合用藥可顯著放緩腫瘤的生長(zhǎng)速度,控制小鼠的體重,保持小鼠的精神狀態(tài)。相對(duì)于單獨(dú)用藥,聯(lián)合用藥在諸多方面優(yōu)勢(shì)明顯。
[Abstract]:Objective to observe the inhibitory effect of Ochitinib combined with dexamethasone on tumor and to analyze the advantages of combined use of omitinib and dexamethasone through cell culture in vitro and tumor-bearing mice. Methods different concentrations of omitinib, dexamethasone and the combination of two drugs were used to treat NSCLC cell line H1975.After 2448h, H1975cells were treated with different concentrations of omitinib and dexamethasone respectively. The inhibition of cell proliferation was detected by MTT colorimetric assay, and the model of lung cancer was established in mice, which was treated with oxitinib, dexamethasone, dexamethasone, dexamethasone, oxitinib, dexamethasone. The tumor volume and body weight of mice were measured continuously in the combination group and control group, and the tumor growth curve and the weight change curve of mice were drawn, respectively. At the same time, the inhibition of HIF-1a and NF- 魏 B related to inflammation and tumor angiogenesis was determined by immunohistochemical S-ABC method. Results the inhibition rate of H1975 cells in single drug group and combined drug group was measured by MTT experiment. The results showed that the inhibition rate of H1975 cell line was compared by SPSS data analysis. There was no significant difference in cell inhibition rate between 24 h and 72 h in different concentration groups of dexamethasone (P > 0.05), but there was significant difference in cell inhibition rate between 24 h and 72 h in different concentration groups of oxetinib (P 鈮，

本文編號(hào)：1595259