姜黄素联合5-FU对胃癌MGC-803细胞抑制作用的实验研究

发布时间：2018-02-14 23:03

本文关键词： 姜黄素 5-FU MGC-803细胞生长抑制细胞凋亡细胞周期实验研究　出处：《湖北中医药大学》2016年硕士论文　论文类型：学位论文

【摘要】：胃癌(gastric cancer)是临床上最常见的消化系统恶性肿瘤之一,我国人群中胃癌的发病率和死亡率都居高不下。在胃癌治疗现有的手段中,化学治疗(化疗)占有重要地位,是晚期胃癌及术后肿瘤复发患者的主要治疗手段。其中氟尿嘧啶(5-FU)是目前胃癌化疗药物的主力之一,其疗效肯定,价格低廉,广泛应用于临床上胃癌治疗的多种化疗药物的联用方案。但5-FU对患者会产生骨髓抑制、恶心呕吐、肝肾功能损伤等较强的毒副作用,严重影响患者的生存质量和后期治疗。由此,积极研发对5-FU具有减毒增效作用的化合物具有重要意义。姜黄素(curcumin)是从我国传统中药姜黄中分离提取的一种多酚类化合物,具有抗肿瘤、抗氧化、抗病毒、抗诱变等多方面的药理作用。其中姜黄素抗肿瘤作用受到国内外学者的广泛重视。本课题探索5-FU与姜黄素联用对体外培养胃癌细胞的生长抑制作用和凋亡诱导作用及其机理。目的:本文旨在研究姜黄素与中、低剂量化疗药5-氟尿嘧啶(5-FU)联用对胃癌MGC-803细胞增殖、细胞凋亡和细胞周期的影响,为临床上应用姜黄素作为胃癌化疗药5-FU的增效剂,以减少5-FU使用剂量、降低其毒副作用提供实验依据。方法:本研究应用MTT法检测姜黄素与5-FU联合对人胃癌MGC-803细胞的抑制作用;应用基于AO/EB双染的荧光显微观察法和Annexin V-FITC/PI双染的流式细胞术检测药物作用对人胃癌MGC-803细胞凋亡的影响;应用基于PI单染的流式细胞术检测姜黄素与5-FU联合对人胃癌MGC-803细胞周期的影响。结果:(1)低剂量(2.4μmol/L)5-FU与姜黄素(25μmol/L)联用组抑制胃癌MGC-803细胞增殖和诱导细胞凋亡的作用显著优于中剂量(4.8μmol/L)5-FU单用组(P0.05);(2)中剂量(4.8μmol/L)5-FU与姜黄素(25μmol/L)联合用药组抑制胃癌MGC-803细胞增殖和诱导细胞凋亡的作用显著优于高剂量(9.6μmol/L)5-FU单用组(P0.05);(3)姜黄素与中剂量或低剂量的5-FU联用可抑制胃癌MGC-803细胞增殖,并诱导细胞凋亡,其作用机制之一是通过阻滞胃癌MGC-803细胞分裂的周期进程,将大量的胃癌细胞阻滞在S期;(4)姜黄素与5-FU联用在抗胃癌细胞方面具有协同作用,并呈现剂量-时间的依赖关系。结论:姜黄素与5-FU联用对体外培养的人胃癌MGC-803细胞的生长与增殖具有显著的抑制作用,并呈现剂量-时间的依赖关系;姜黄素可以显著增强5-FU对胃癌MGC-803细胞的生长抑制作用和凋亡诱导作用;姜黄素可显著增强5-FU对胃癌细胞MGC-803在细胞周期S期的阻滞。本研究结果为临床上应用姜黄素作为5-FU治疗胃癌的辅助用药,以减少5-FU的使用剂量,从而降低其毒副作用提供了实验依据。
[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.
【学位授予单位】：湖北中医药大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R735.2

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