本文選題：姜黃素 + 納米粒�。� 參考：《第三軍醫(yī)大學(xué)》2015年碩士論文

【摘要】：背景肺癌是發(fā)病率及死亡率最高的惡性腫瘤,且其發(fā)病率有增加趨勢�；熕幬锏哪退幮约案弊饔迷斐赡壳胺伟┗煹男Ч焕硐�。近年來從傳統(tǒng)中藥姜黃中提取的姜黃素(curcumin,Cur)成為研究熱點(diǎn),初步研究證實(shí)Cur對肺癌、乳腺癌、肝癌等癌癥有抑制作用,而且具有副作用小、價格低廉的優(yōu)點(diǎn)。然而Cur因不穩(wěn)定和其水溶性差的特點(diǎn),限制了其臨床應(yīng)用。采用藥物制劑技術(shù),制成納米粒,可以提高Cur的水溶性及穩(wěn)定性。本研究采用新型姜黃素納米粒(curcumin nanoparticles,Cur-NPs)作為研究對象,在體內(nèi)外考察其對Lewis肺癌增殖的影響。目的通過體內(nèi)外實(shí)驗(yàn)考察Cur-NPs對Lewis肺癌增殖的影響,并初步探討Cur誘導(dǎo)Lewis肺癌凋亡的可能機(jī)制。研究方法1.MTT法測定不同濃度的Cur-NPs及Cur對Lewis細(xì)胞的增殖抑制作用。2.流式細(xì)胞術(shù)測定Cur-NPs及Cur對Lewis細(xì)胞周期、凋亡、細(xì)胞內(nèi)鈣離子濃度、細(xì)胞內(nèi)活性氧及線粒體膜電位的影響。3.建立C57BL/6J小鼠Lewis肺癌模型,考察Cur-NPs及Cur對Lewis肺癌的抑瘤作用。4.Western blot測定Cur在體內(nèi)外對Lewis肺癌中Akt、Fox O1及Bim蛋白的影響。結(jié)果1.Cur-NPs及Cur均可抑制Lewis肺癌的增殖,24h的IC50分別為:10.65μmol/L及34.91μmol/L。2.Cur組和Cur-NPs組抑制Lewis細(xì)胞周期于S期比例分別為(81.57±9.15)%、(92.20±7.65)%。Cur組和Cur-NPs誘導(dǎo)Lewis肺癌細(xì)胞凋亡比例分別為(7.43±1.13)%、(67.69±9.86)%。Cur組和Cur-NPs組作用Lewis肺癌細(xì)胞后細(xì)胞內(nèi)活性氧濃度分別為(2088.01±238.19)、(2568.67±361.85)。Cur組和Cur-NPs組作用Lewis肺癌細(xì)胞后細(xì)胞內(nèi)鈣離子濃度分別為(52.11±11.28)、(97.85±15.68)。Cur組和Cur-NPs組作用Lewis肺癌細(xì)胞后線粒體膜電位分別為(128.97±18.56)、(94.00±12.11)。因此Cur-NPs及Cur均可阻滯Lewis肺癌細(xì)胞周期于S期,誘導(dǎo)Lewis肺癌細(xì)胞凋亡,升高細(xì)胞內(nèi)鈣離子濃度,升高細(xì)胞內(nèi)活性氧濃度,降低細(xì)胞線粒體膜電位,且Cur-NPs作用更強(qiáng)(P0.05)。3.給藥14天后,處死小鼠,解剖腫瘤稱重后,Ct組、Cur組、Cur-NPs和NPs組的瘤重分別為(4.10±0.31)g、(2.50±0.27)g、(1.40±0.19)g和(4.04±0.32)g。Cur組、Cur-NPs組的抑瘤率分別為(39.02±7.63)%和(65.85±10.81)%。因此Cur-NPs及Cur均可抑制小鼠Lewis肺癌的生長,且Cur-NPs抑制生長作用更強(qiáng)(P0.05)。4.Cur在體內(nèi)外抑制Akt的表達(dá),促進(jìn)Fox O1及Bim的表達(dá)(P0.05)。結(jié)論一、在體外Cur-NPs可以明顯地增強(qiáng)Cur抑制Lewis肺癌細(xì)胞增殖、阻滯細(xì)胞周期于S期、誘導(dǎo)凋亡、增高細(xì)胞內(nèi)鈣離子濃度、增高細(xì)胞內(nèi)活性氧及降低細(xì)胞線粒體膜電位的能力,在體內(nèi)Cur-NPs可以明顯地增強(qiáng)Cur抑制Lewis肺癌生長的能力。Cur-NPs可增強(qiáng)Cur對Lewis肺癌細(xì)胞增殖和腫瘤生長的抑制作用。二、Cur可能通過PI3K/Akt-FoxO1-Bim信號通路誘導(dǎo)Lewis肺癌凋亡。
[Abstract]:Background Lung cancer is a malignant tumor with the highest morbidity and mortality. The drug resistance and side effects of chemotherapeutic drugs cause the effect of chemotherapy in lung cancer is not ideal. Curcumin (Curcumin Curcumin) extracted from traditional Chinese medicine turmeric has become a research hotspot in recent years. Preliminary studies have proved that Cur has inhibitory effect on lung cancer, breast cancer and liver cancer, and has the advantages of low side effect and low price. However, the clinical application of Cur is limited by its instability and poor water solubility. The water solubility and stability of Cur can be improved by using pharmaceutical preparation technology to prepare nanoparticles. The effect of curcumin nanoparticles-Cur-NPs on the proliferation of Lewis lung cancer was investigated in vitro and in vivo. Objective to investigate the effect of Cur-NPs on the proliferation of Lewis lung cancer in vitro and in vivo, and to explore the possible mechanism of Lewis lung cancer apoptosis induced by Cur. Methods 1.MTT assay was used to determine the inhibitory effects of Cur-NPs and Cur on the proliferation of Lewis cells. The effects of Cur-NPs and Cur on the cell cycle, apoptosis, intracellular calcium concentration, intracellular reactive oxygen species and mitochondrial membrane potential were determined by flow cytometry. C57BL/6J mouse model of Lewis lung cancer was established to investigate the inhibitory effect of Cur-NPs and Cur on Lewis lung cancer. 4. Western blot was used to determine the effect of Cur on the expression of AkttFox O1 and Bim protein in Lewis lung cancer in vitro and in vivo. Results both 1.Cur-NPs and Cur could inhibit the proliferation of Lewis lung cancer for 24 hours, and the ratio of inhibition of Lewis cell cycle in S phase was 81.57 鹵9.15 鹵7.65)%.Cur and Cur-NPs induced Lewis lung cancer cell apoptosis was 7.43 鹵1.1367.69 鹵9.86)%.Cur and Cur-NPs respectively in the group of 10. 65 渭 mol/L and 34.91 渭 mol/L.2.Cur and Cur-NPs. The intracellular concentration of reactive oxygen species (Ros) was 2088.01 鹵238.19 (2568.67 鹵361.85).Cur) and (52.11 鹵11.28) (97.85 鹵15.68).Cur) in Lewis lung cancer cells and 128.97 鹵18.56 (12.11 鹵12.11) in Cur-NPs group respectively. Therefore, both Cur-NPs and Cur can block the cell cycle of Lewis lung cancer cells in S phase, induce apoptosis of Lewis lung cancer cells, increase intracellular calcium concentration, increase intracellular reactive oxygen species concentration, and decrease mitochondrial membrane potential of Lewis lung cancer cells, and Cur-NPs has a stronger effect on Lewis lung cancer cells. After 14 days of administration, the mice were killed. The tumor inhibition rates of Cur-NPs and NPs in curr group and NPs group were 4.10 鹵0.31, 2.50 鹵0.27, 1.40 鹵0.19g and 4.04 鹵4.04 鹵0.32)g.Cur, respectively. The tumor inhibition rates of Cur-NPs group were 39.02 鹵7.63% and 65.85 鹵10.81%, respectively. Therefore, both Cur-NPs and Cur could inhibit the growth of mouse Lewis lung cancer, and Cur-NPs inhibited the expression of Akt more strongly in vitro and in vivo, and promoted the expression of Fox O1 and Bim. Conclusion: in vitro, Cur-NPs can significantly enhance the ability of Cur to inhibit the proliferation of Lewis lung cancer cells, block cell cycle in S phase, induce apoptosis, increase intracellular calcium concentration, increase intracellular reactive oxygen species and decrease mitochondrial membrane potential. In vivo, Cur-NPs significantly enhanced the ability of Cur to inhibit the growth of Lewis lung cancer. Cur-NPs enhanced the inhibitory effect of Cur on the proliferation and tumor growth of Lewis lung cancer cells. Cur may induce apoptosis of Lewis lung cancer through PI3K/Akt-FoxO1-Bim signaling pathway.
【學(xué)位授予單位】：第三軍醫(yī)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R734.2

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本文編號：1908375