本文關(guān)鍵詞： 姜黃素 5-FU MGC-803細(xì)胞 生長(zhǎng)抑制 細(xì)胞凋亡 細(xì)胞周期 實(shí)驗(yàn)研究　出處：《湖北中醫(yī)藥大學(xué)》2016年碩士論文　論文類型：學(xué)位論文

【摘要】：胃癌(gastric cancer)是臨床上最常見(jiàn)的消化系統(tǒng)惡性腫瘤之一,我國(guó)人群中胃癌的發(fā)病率和死亡率都居高不下。在胃癌治療現(xiàn)有的手段中,化學(xué)治療(化療)占有重要地位,是晚期胃癌及術(shù)后腫瘤復(fù)發(fā)患者的主要治療手段。其中氟尿嘧啶(5-FU)是目前胃癌化療藥物的主力之一,其療效肯定,價(jià)格低廉,廣泛應(yīng)用于臨床上胃癌治療的多種化療藥物的聯(lián)用方案。但5-FU對(duì)患者會(huì)產(chǎn)生骨髓抑制、惡心嘔吐、肝腎功能損傷等較強(qiáng)的毒副作用,嚴(yán)重影響患者的生存質(zhì)量和后期治療。由此,積極研發(fā)對(duì)5-FU具有減毒增效作用的化合物具有重要意義。姜黃素(curcumin)是從我國(guó)傳統(tǒng)中藥姜黃中分離提取的一種多酚類化合物,具有抗腫瘤、抗氧化、抗病毒、抗誘變等多方面的藥理作用。其中姜黃素抗腫瘤作用受到國(guó)內(nèi)外學(xué)者的廣泛重視。本課題探索5-FU與姜黃素聯(lián)用對(duì)體外培養(yǎng)胃癌細(xì)胞的生長(zhǎng)抑制作用和凋亡誘導(dǎo)作用及其機(jī)理。目的:本文旨在研究姜黃素與中、低劑量化療藥5-氟尿嘧啶(5-FU)聯(lián)用對(duì)胃癌MGC-803細(xì)胞增殖、細(xì)胞凋亡和細(xì)胞周期的影響,為臨床上應(yīng)用姜黃素作為胃癌化療藥5-FU的增效劑,以減少5-FU使用劑量、降低其毒副作用提供實(shí)驗(yàn)依據(jù)。方法:本研究應(yīng)用MTT法檢測(cè)姜黃素與5-FU聯(lián)合對(duì)人胃癌MGC-803細(xì)胞的抑制作用;應(yīng)用基于AO/EB雙染的熒光顯微觀察法和Annexin V-FITC/PI雙染的流式細(xì)胞術(shù)檢測(cè)藥物作用對(duì)人胃癌MGC-803細(xì)胞凋亡的影響;應(yīng)用基于PI單染的流式細(xì)胞術(shù)檢測(cè)姜黃素與5-FU聯(lián)合對(duì)人胃癌MGC-803細(xì)胞周期的影響。結(jié)果:(1)低劑量(2.4μmol/L)5-FU與姜黃素(25μmol/L)聯(lián)用組抑制胃癌MGC-803細(xì)胞增殖和誘導(dǎo)細(xì)胞凋亡的作用顯著優(yōu)于中劑量(4.8μmol/L)5-FU單用組(P0.05);(2)中劑量(4.8μmol/L)5-FU與姜黃素(25μmol/L)聯(lián)合用藥組抑制胃癌MGC-803細(xì)胞增殖和誘導(dǎo)細(xì)胞凋亡的作用顯著優(yōu)于高劑量(9.6μmol/L)5-FU單用組(P0.05);(3)姜黃素與中劑量或低劑量的5-FU聯(lián)用可抑制胃癌MGC-803細(xì)胞增殖,并誘導(dǎo)細(xì)胞凋亡,其作用機(jī)制之一是通過(guò)阻滯胃癌MGC-803細(xì)胞分裂的周期進(jìn)程,將大量的胃癌細(xì)胞阻滯在S期;(4)姜黃素與5-FU聯(lián)用在抗胃癌細(xì)胞方面具有協(xié)同作用,并呈現(xiàn)劑量-時(shí)間的依賴關(guān)系。結(jié)論:姜黃素與5-FU聯(lián)用對(duì)體外培養(yǎng)的人胃癌MGC-803細(xì)胞的生長(zhǎng)與增殖具有顯著的抑制作用,并呈現(xiàn)劑量-時(shí)間的依賴關(guān)系;姜黃素可以顯著增強(qiáng)5-FU對(duì)胃癌MGC-803細(xì)胞的生長(zhǎng)抑制作用和凋亡誘導(dǎo)作用;姜黃素可顯著增強(qiáng)5-FU對(duì)胃癌細(xì)胞MGC-803在細(xì)胞周期S期的阻滯。本研究結(jié)果為臨床上應(yīng)用姜黃素作為5-FU治療胃癌的輔助用藥,以減少5-FU的使用劑量,從而降低其毒副作用提供了實(shí)驗(yàn)依據(jù)。
[Abstract]:Gastric cancer is one of the most common malignant tumors of digestive system in clinic. The morbidity and mortality of gastric cancer in Chinese population are very high. Chemotherapy plays an important role in the treatment of gastric cancer. Fluorouracil 5-FU is one of the main chemotherapeutic drugs for gastric cancer. A wide range of chemotherapeutic regimens are widely used in the treatment of gastric cancer. However, 5-FU can produce strong side effects such as bone marrow suppression, nausea and vomiting, liver and kidney function damage, etc. As a result, it is of great significance to develop compounds with attenuated and synergistic effects on 5-FU. Curcumin is a polyphenolic compound isolated from turmeric, a traditional Chinese medicine, which is isolated from Chinese traditional Chinese medicine turmeric. Has anti-tumor, anti-oxidation, anti-virus, The antimutagenic effect of curcumin has been paid more and more attention by domestic and foreign scholars. In this paper, we studied the effect of 5-FU combined with curcumin on the growth inhibition and apoptosis induction of gastric cancer cells cultured in vitro. Objective: to study curcumin and its mechanism. The effects of low dose 5-fluorouracil 5-FU (5-FU) on the proliferation, apoptosis and cell cycle of gastric cancer MGC-803 cells. Curcumin was used as a synergist of 5-FU in order to reduce the dosage of 5-FU. Methods: MTT assay was used to detect the inhibitory effect of curcumin combined with 5-FU on human gastric cancer MGC-803 cells. Fluorescence microscopy based on AO/EB double staining and flow cytometry with Annexin V-FITC / Pi double staining were used to detect the effect of drugs on apoptosis of human gastric cancer MGC-803 cells. The effect of curcumin combined with 5-FU on the cell cycle of human gastric cancer MGC-803 cells was detected by flow cytometry based on Pi single staining. Results the effects of low dose of curcumin on the proliferation and apoptosis of gastric cancer MGC-803 cells were observed in combination with low dose of 2. 4 渭 mol/L)5-FU and curcumin 25 渭 mol / L). The effect of inhibiting proliferation and inducing apoptosis of gastric cancer MGC-803 cells in combination of moderate dose of 4. 8 渭 mol/L)5-FU and curcumin 25 渭 mol / L) was better than that of high dose of 9. 6 渭 mol/L)5-FU alone group (P0. 05 P0. 05) of curcumin combined with medium or low dose of 5 Fu. The effect of curcumin combined with medium or low dose of 5 Fu was significantly better than that of high dose of 9. 6 渭 mol/L)5-FU alone in inhibiting proliferation and inducing apoptosis of gastric cancer MGC-803 cells. To inhibit the proliferation of gastric cancer MGC-803 cells, One of the mechanisms of inducing apoptosis is to block the cell cycle of gastric cancer MGC-803 cells and block a large number of gastric cancer cells in S phase.) curcumin combined with 5-FU has synergistic effect on gastric cancer cells. Conclusion: the combination of curcumin and 5-FU can significantly inhibit the growth and proliferation of human gastric cancer MGC-803 cells in vitro and present a dose-time dependent relationship. Curcumin could significantly enhance the growth inhibition and apoptosis induction of MGC-803 cells induced by 5-FU. Curcumin could significantly enhance the blocking of 5-FU on MGC-803 of gastric cancer cells in S phase of cell cycle. The results showed that curcumin could be used as an adjuvant in the treatment of gastric cancer in order to reduce the dosage of 5-FU. Therefore, the experimental basis is provided to reduce the toxicity and side effects.
【學(xué)位授予單位】：湖北中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R735.2

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