發(fā)布時(shí)間：2018-09-11 10:18

【摘要】：目的：探討雙氫青蒿素（DHA）對PC-3和DU145細(xì)胞遷移和侵襲能力的影響及其可能機(jī)制。 方法：第一部分：不同濃度（0μmol·L-1、25μmol·L-1、50μmol·L-1和100μmol·L-1）的DHA分別作用于PC-3和DU145細(xì)胞48h后，運(yùn)用細(xì)胞劃痕實(shí)驗(yàn)和侵襲實(shí)驗(yàn)檢測細(xì)胞的遷移和侵襲能力。提取各組細(xì)胞的總mRNA和蛋白，分別進(jìn)行熒光定量PCR和Western blot實(shí)驗(yàn)，檢測Vimentin和CDH1的轉(zhuǎn)錄和表達(dá)水平。第二部分：采用人前列腺癌PC-3和DU145細(xì)胞建立裸鼠種植瘤模型，18只模型鼠隨機(jī)分為對照組、DMSO組（二甲基亞砜1mL/kg）、DHA組(DHA200μmol/kg），經(jīng)13天干預(yù)后，免疫組織（SP）化學(xué)法檢測侵襲相關(guān)基因Vimentin和CDH1的表達(dá)水平。 結(jié)果：不同濃度（25μmol·L-1、50μmol·L-1和100μmol·L-1）的DHA均能顯著抑制PC-3和DU145遷移和侵襲能力（P0.05），與對照組比較，不同濃度的DHA均能顯著抑制Vimentin和促進(jìn)CDH1的轉(zhuǎn)錄和表達(dá)水平（P0.05）。25μmol·L-1的DHA抑制Vimentin和促進(jìn)CDH1蛋白的表達(dá)最為明顯。免疫組化結(jié)果顯示，在兩種細(xì)胞中，，DHA組CDH1的表達(dá)均高于對照組和溶劑組（P0.05）；Vimentin的表達(dá)均低于對照組和溶劑組（P0.05）。 結(jié)論：不同濃度的DHA干預(yù)后能顯著抑制PC-3和DU145細(xì)胞的遷移和侵襲能力，而在體腫塊生長速度受抑制進(jìn)一步證實(shí)DHA具有抑制癌細(xì)胞遷移和侵襲能力。而從免疫印跡和免疫組化結(jié)果我們推測DHA可能通過干擾Vimentin和CDH1蛋白的表達(dá)相關(guān)而起到抑制癌細(xì)胞遷移和侵襲的效果。
[Abstract]:Aim: to investigate the effect of dihydroartemisinin (DHA) on migration and invasion of PC-3 and DU145 cells and its possible mechanism. Methods: in the first part, the cells of PC-3 and DU145 were treated with different concentrations of DHA (0 渭 mol L -1, 25 渭 mol L -1, 50 渭 mol L -1 and 100 渭 mol L -1) for 48 h, respectively. Cell scratch assay and invasion assay were used to detect the migration and invasion ability of the cells. The total mRNA and protein were extracted from the cells of each group, and the transcription and expression levels of Vimentin and CDH1 were detected by fluorescence quantitative PCR and Western blot assay. Part two: PC-3 and DU145 cells were used to establish implanted tumor model in nude mice. Eighteen nude mice were randomly divided into two groups: control group (1mL/kg) (DHA200 渭 mol/kg). Immunohistochemical (SP) method was used to detect the expression of Vimentin and CDH1. Results: DHA at different concentrations (25 渭 mol L-1 and 100 渭 mol L-1) significantly inhibited the migration and invasion of PC-3 and DU145 (P0.05), compared with the control group. DHA at different concentrations could significantly inhibit Vimentin and promote the transcription and expression of CDH1 (P0.05) .25 渭 mol L-1 DHA could inhibit Vimentin and promote CDH1 protein expression. Immunohistochemical results showed that the expression of CDH1 in DHA group was higher than that in control group and solvent group (P0.05), and the expression of Vimentin was lower than that in control group and solvent group (P0.05). Conclusion: different concentrations of DHA can significantly inhibit the migration and invasion of PC-3 and DU145 cells, and the inhibition of tumor growth rate in vivo further confirms that DHA can inhibit the migration and invasion of cancer cells. From the results of immunoblotting and immunohistochemistry we speculate that DHA may inhibit the migration and invasion of cancer cells by interfering with the expression of Vimentin and CDH1 proteins.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R737.25

【參考文獻(xiàn)】

相關(guān)期刊論文 前9條

1 李慶春;高小玲;鄒聰;石之虎;李劍;羅子國;;雙氫青蒿素對前列腺癌PC-3細(xì)胞體內(nèi)生長及Caspase-3表達(dá)的影響[J];第四軍醫(yī)大學(xué)學(xué)報(bào);2009年05期

2 陳衛(wèi)強(qiáng),戚好文,吳昌歸,崔燕,劉斌,李焰,吳軍正;雙氫青蒿素抗人肺腺癌A549細(xì)胞生長的實(shí)驗(yàn)研究[J];中國肺癌雜志;2005年02期

3 Jun Yu;Wu Zhang;Feng Gao;Yuan-Xing Liu;Zhi-Yun Chen;Long-Yu Cheng;Shang-Fen Xie;Shu-Sen Zheng;;FBW7 increases chemosensitivity in hepatocellular carcinoma cells through suppression of epithelial-mesenchymal transition[J];Hepatobiliary & Pancreatic Diseases International;2014年02期

4 劉春朝,王玉春,歐陽藩,葉和春,李國風(fēng);青蒿素研究進(jìn)展[J];化學(xué)進(jìn)展;1999年01期

5 李劍;王紅;范京川;王婧;羅子國;;雙氫青蒿素對前列腺癌裸鼠種植瘤CHOP表達(dá)的影響[J];激光雜志;2011年06期

6 穆德廣;戚好文;金發(fā)光;孫瑞琳;;雙氫青蒿素誘導(dǎo)肺癌SPC-A-1細(xì)胞周期阻滯的研究[J];實(shí)用醫(yī)學(xué)雜志;2011年03期

7 郭燕;王俊;陳正堂;;青蒿素類藥物的藥理作用新進(jìn)展[J];中國臨床藥理學(xué)與治療學(xué);2006年06期

8 葉定偉;李長嶺;;前列腺癌發(fā)病趨勢的回顧和展望[J];中國癌癥雜志;2007年03期

9 耿云震;王勝強(qiáng);楊杰;王文杰;;雙氫青蒿素對雄激素非依賴性前列腺癌細(xì)胞中mTOR表達(dá)和分布的影響[J];中國現(xiàn)代醫(yī)學(xué)雜志;2011年18期

相關(guān)博士學(xué)位論文 前1條

1 劉欣;CXCR1/CXCR2受體拮抗劑-G31P對前列腺癌的抑制作用及機(jī)制研究[D];大連醫(yī)科大學(xué);2012年

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