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

【摘要】：背景和目的:鼻咽癌是南中國(guó)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(dá)50%以上。然而,不管是放射治療或化學(xué)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(diǎn)問題。由于腫瘤的遠(yuǎn)處轉(zhuǎn)移和放射的局部損傷作用給進(jìn)一步改善晚期鼻咽癌患者的預(yù)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(dú)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(dǎo)化合物,通過化學(xué)合成方法對(duì)其結(jié)構(gòu)進(jìn)行改造,合成了20個(gè)結(jié)構(gòu)新穎的苦參堿衍生物,并進(jìn)行了抗鼻咽癌作用篩選�？鄥A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(shí)驗(yàn)研究了該藥對(duì)人鼻咽癌細(xì)胞CNE2體外增殖的影響,并探討其機(jī)制。 方法:選用鼻咽癌細(xì)胞株CNE2進(jìn)行實(shí)驗(yàn),首先經(jīng)MTT進(jìn)行抗鼻咽癌作用篩選;然后本實(shí)驗(yàn)分四組即是實(shí)驗(yàn)組、陰性對(duì)照組、正常細(xì)胞對(duì)照組、溶劑組、空白對(duì)照組(調(diào)零孔);倒置光學(xué)顯微鏡下觀察細(xì)胞形態(tài);MTT實(shí)驗(yàn)檢測(cè)藥物抑制率;流式細(xì)胞儀檢測(cè)細(xì)胞周期的分布和凋亡情況。 結(jié)果:加藥細(xì)胞組形態(tài)變圓、變小、胞內(nèi)可見空泡;MTT檢測(cè)可見藥物對(duì)人鼻咽癌細(xì)胞株CNE2有顯著的抑制作用(P0.05),抑制率最大可達(dá)到97.9%,但是對(duì)人臍靜脈內(nèi)皮細(xì)胞沒有表顯出相應(yīng)的抑制作用,抑制率最大僅達(dá)到7.7%;流式細(xì)胞儀檢測(cè)結(jié)果可見CNE2細(xì)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(dá)89.71%。 結(jié)論:體外實(shí)驗(yàn)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(xì)胞周期S期阻滯和誘導(dǎo)細(xì)胞凋亡來抑制鼻咽癌細(xì)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(xué)位授予單位】：廣西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2011
【分類號(hào)】：R739.63

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