本文選題：14-噻吩基次亞甲基苦參堿 + CNE2細胞��； 參考：《廣西醫(yī)科大學》2011年碩士論文

【摘要】：背景和目的:鼻咽癌是南中國地區(qū)常見的頭頸部腫瘤,治療上推薦以放療為主結(jié)合化療的綜合治療方法,五年生存率可達50%以上。然而,不管是放射治療或化學治療均有一定的毒副作用,如何提高放化療效果并減少放療后并發(fā)癥和減輕放療的毒副作用是鼻咽癌研究關(guān)注的熱點問題。由于腫瘤的遠處轉(zhuǎn)移和放射的局部損傷作用給進一步改善晚期鼻咽癌患者的預后和生活質(zhì)量帶來了困難,因此需要越來越多的化療手段介入�？鄥A是近年受到關(guān)注的抗腫瘤成分,但存在生物利用率不高,并且有一定的毒副作用,使其難以單獨用于臨床抗腫瘤治療。為了使苦參堿毒性降低和生物利用度更高,我們的合作者以苦參堿為先導化合物,通過化學合成方法對其結(jié)構(gòu)進行改造,合成了20個結(jié)構(gòu)新穎的苦參堿衍生物,并進行了抗鼻咽癌作用篩選。苦參堿改構(gòu)體14-噻吩基次亞甲基苦參堿正是從中初步篩出的具有抗腫瘤活性的成分,本實驗研究了該藥對人鼻咽癌細胞CNE2體外增殖的影響,并探討其機制。 方法:選用鼻咽癌細胞株CNE2進行實驗,首先經(jīng)MTT進行抗鼻咽癌作用篩選;然后本實驗分四組即是實驗組、陰性對照組、正常細胞對照組、溶劑組、空白對照組(調(diào)零孔);倒置光學顯微鏡下觀察細胞形態(tài);MTT實驗檢測藥物抑制率;流式細胞儀檢測細胞周期的分布和凋亡情況。 結(jié)果:加藥細胞組形態(tài)變圓、變小、胞內(nèi)可見空泡;MTT檢測可見藥物對人鼻咽癌細胞株CNE2有顯著的抑制作用(P0.05),抑制率最大可達到97.9%,但是對人臍靜脈內(nèi)皮細胞沒有表顯出相應的抑制作用,抑制率最大僅達到7.7%;流式細胞儀檢測結(jié)果可見CNE2細胞的周期阻滯在S期和有濃度依賴性的明顯凋亡,凋亡率最大可達89.71%。 結(jié)論:體外實驗表明,14-噻吩基次亞甲基苦參堿具有明顯的抗鼻咽癌作用,可通過細胞周期S期阻滯和誘導細胞凋亡來抑制鼻咽癌細胞的增殖分裂,并表現(xiàn)出很弱的毒性。
[Abstract]:Background and objective: nasopharyngeal carcinoma (NPC) is a common head and neck tumor in South China. Radiotherapy combined with chemotherapy is recommended. The 5-year survival rate is over 50%. However, both radiotherapy and chemotherapy have some side effects. How to improve the effect of radiotherapy and chemotherapy, reduce the complications after radiotherapy and reduce the side effects of radiotherapy is a hot issue in the research of nasopharyngeal carcinoma. Because the distant metastasis of the tumor and the local injury of radiation bring difficulties to further improve the prognosis and quality of life of the patients with advanced nasopharyngeal carcinoma, more and more chemotherapy interventions are needed. Matrine is an antitumor component that has attracted much attention in recent years, but its bioavailability is not high, and it has some toxic side effects, which makes it difficult to be used in clinical antitumor therapy alone. In order to reduce the toxicity and increase the bioavailability of matrine, our collaborators modified the structure of matrine by chemical synthesis method, and synthesized 20 novel matrine derivatives. The anti-nasopharyngeal carcinoma was screened. Matrine modified by 14 thienyl methylene matrine is a primary antitumor component. The effect of matrine on the proliferation of human nasopharyngeal carcinoma (NPC) cell line CNE2 in vitro was studied and its mechanism was discussed. Methods: the nasopharyngeal carcinoma cell line CNE2 was selected for the experiment, and the anti-nasopharyngeal carcinoma action was screened by MTT, then the experiment was divided into four groups: experimental group, negative control group, normal cell control group and solvent group. In the blank control group, the cell morphology and MTT assay were observed under inverted optical microscope, and the cell cycle distribution and apoptosis were detected by flow cytometry. Results: the morphology of the cells in the drug added group became round and small. MTT assay showed that the drug had a significant inhibitory effect on human nasopharyngeal carcinoma (NPC) cell line CNE2, with a maximum inhibition rate of 97.9%, but it had no apparent inhibitory effect on human umbilical vein endothelial cells (HUVEC). The inhibition rate was only 7.7.The results of flow cytometry showed that CNE2 cell cycle arrest was obvious in S phase and concentration-dependent manner, and the maximum apoptosis rate was 89.71%. Conclusion: the results of in vitro experiments showed that tetrathiophenyl methylene matrine could inhibit the proliferation and division of nasopharyngeal carcinoma cells through cell cycle S phase arrest and apoptosis, and showed a weak toxicity.
【學位授予單位】：廣西醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2011
【分類號】：R739.63

【參考文獻】

相關(guān)期刊論文 前10條

1 萬旭英,陳哲;苦參堿注射液聯(lián)合TACE術(shù)治療原發(fā)性肝癌的臨床觀察[J];浙江中醫(yī)學院學報;2002年02期

2 何松;左國慶;張燕;湯為學;;苦參堿對肝癌細胞HepG2端粒酶活性調(diào)控的體外研究[J];重慶醫(yī)學;2008年03期

3 李毓,胡祖光,胡笑克;薏苡仁酯對人鼻咽癌細胞周期的影響[J];華夏醫(yī)學;2004年02期

4 謝強;趙蕩;劉興京;黃作平;鄒冰心;王立根;;復方苦參注射液聯(lián)合適形調(diào)強放療治療鼻咽癌的臨床研究[J];國際內(nèi)科學雜志;2008年03期

5 熊暢;涂明利;劉先軍;羅強;聞心培;;苦參堿對A549細胞增殖和PinX1 mRNA表達的影響[J];華南國防醫(yī)學雜志;2007年05期

6 王利民;苦參堿誘導骨肉瘤細胞凋亡的實驗研究[J];實用診斷與治療雜志;2004年05期

7 楊澤松;陳建斌;牟君;張紅賓;唐曉瓊;胡妮妮;黃宗干;;苦參堿抑制U937細胞增殖與誘導凋亡的體外實驗研究[J];江西醫(yī)學院學報;2007年03期

8 沈蕾;細胞凋亡與腫瘤的關(guān)系[J];臨床兒科雜志;2002年10期

9 趙充;管迅行;;鼻咽癌放化綜合治療臨床研究現(xiàn)狀[J];中華腫瘤防治雜志;2006年06期

10 王震宇;王榮富;韓士群;劉愛琴;;天然抗腫瘤藥苦參堿的研究與開發(fā)[J];食品與藥品;2007年06期

，

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