氧化苦参碱通过TGFβ1/P38/PAI-1信号通路逆转结肠癌上皮间质化及耐药的机制研究
发布时间：2021-10-21 22:36
目的:本课题研究拟以结肠癌细胞和构建结肠癌耐药细胞模型为基础,借助分子生物学及细胞生物学等先进技术,通过体外实验探讨氧化苦参碱对结肠癌细胞和结肠癌耐药细胞中TGF-β1/P38/PAI-1信号通路的干预作用,同时探索结肠癌上皮间质化（Epithelial-mesenchymal transition,EMT）对结肠癌耐药转移的作用机制,并以此来阐明氧化苦参碱逆转结肠癌EMT改变的分子机制及氧化苦参碱的抗肿瘤效用,为逆转结肠癌多药耐药提供新的研究方向。材料与方法:1.检测氧化苦参碱对于结肠癌细胞EMT的作用及迁移能力的影响。1.1对HT-29细胞和RKO细胞随机分组,以正常结肠上皮细胞FHC细胞作为对照组。使用Western blots方法分别检测各组细胞的EMT的相关标志物,包括上皮细胞标志物钙粘附蛋白E（E-cadherin）和间充质细胞标志物α平滑肌肌动蛋白（Alpha-smooth muscle actin,α-SMA）、纤连蛋白（fibronectin,FN）、纤溶酶原激活物抑制剂-1（Plasminogen Act ivat inhibitor-1,PAI-1）在内的蛋白表达...
【文章来源】：辽宁中医药大学辽宁省
【文章页数】：110 页
【学位级别】：博士
【部分图文】：
结肠癌细胞发生EMT改变
.氧化苦参碱分子结构（oxymatrinere 2. The molecular structure of oxy氧化苦参碱对 RKO 细胞增殖的抑制ect of oxymatrine on the proliferatio24 h 48 h 4.07±1.39 4.64±2.45 6.39±2.17 7.76±4.3 11.48±2.8118.22±5.18a28.91±1.1a38.22±3.86a46.75±5.23a51.05±5.67a55.51±2.6a63.34±7a69.74±3.19a74.63±3.92a85.88±3.59a87.74±3.02a组 (OM 0 mg/mL).
图 2.氧化苦参碱分子结构（oxymatrine，OM）Figure 2. The molecular structure of oxymatrine.表 1 氧化苦参碱对 RKO 细胞增殖的抑制率(%)Table 1. The inhibitory effect of oxymatrine on the proliferation inhibition of RKOM(mg/mL) 24 h 48 h 72 h0.125 4.07±1.39 4.64±2.45 5.46±1.320.25 6.39±2.17 7.76±4.3 11.54±6.120.5 11.48±2.8118.22±5.18a25.43±2.88a128.91±1.1a38.22±3.86a39.01±4.01a246.75±5.23a51.05±5.67a51.75±0.75a455.51±2.6a63.34±7a67.94±2.7a869.74±3.19a74.63±3.92a74.56±3.74a2085.88±3.59a87.74±3.02a90.33±2.28aaP < 0.05 vs. 对照组 (OM 0 mg/mL).
【参考文献】：
期刊论文
[1]氧化苦参碱抑制DBTC刺激的胰腺腺泡细胞中上皮间质转化相关蛋白及TβRⅡ和p-Smad2/3表达[J]. 张斌,许威,李如月,张青,向晓辉,夏时海. 遵义医学院学报. 2017(05)
[2]氧化苦参碱干预TGF-β1诱导A549细胞上皮-间质转化作用研究[J]. 刘蕾,马壮,谢华,孙文武. 陕西医学杂志. 2016(11)
[3]Effect of h GC-MSCs from human gastric cancer tissue on cell proliferation, invasion and epithelial-mesenchymal transition in tumor tissue of gastric cancer tumor-bearing mice[J]. Lin Song,Xin Zhou,Hong-Jun Jia,Mei Du,Jin-Ling Zhang,Liang Li. Asian Pacific Journal of Tropical Medicine. 2016(08)
[4]Dexamethasone inhibits hypoxia-induced epithelial-mesenchymal transition in colon cancer[J]. Jung Ho Kim,You-Jin Hwang,Sang Hoon Han,Young Eun Lee,Saerom Kim,Yoon Jae Kim,Jae Hee Cho,Kwang An Kwon,Ju Hyun Kim,Se-Hee Kim. World Journal of Gastroenterology. 2015(34)
[5]Epithelial-mesenchymal, mesenchymal-epithelial, and endothelial-mesenchymal transitions in malignant tumors: An update[J]. Simona Gurzu,Sabin Turdean,Attila Kovecsi,Anca Otilia Contac,Ioan Jung. World Journal of Clinical Cases. 2015(05)
[6]氧化苦参碱抑制高糖诱导的大鼠肾小管上皮-间充质转化及其机制研究[J]. 刘丽荣,李霜,王圆圆,石明隽,肖瑛,郭兵. 中国病理生理杂志. 2013(12)
[7]Oxymatrine liposome attenuates hepatic fibrosis via targeting hepatic stellate cells[J]. Ning-Li Chai,Hui Shi,Chang-Hao Cai,Jun Wan,Shi-Ping Xu,Ben-Yan Wu,Department of Gastroenterology,South Building of Chinese People’s Liberation Army General Hospital,Beijing 100853,China Qiang Fu,Department of Gastroenterology,Xi’an Children’s Hospital,Xi’an 710002,Shaanxi Province,China. World Journal of Gastroenterology. 2012(31)
[8]氧化苦参碱对人胃癌MGC-803细胞裸鼠皮下移植瘤形态学影响的作用[J]. 孙宁,徐玉芳,刘粉霞. 中医学报. 2010(06)
[9]Antitumor effect of matrine in human hepatoma G2 cells by inducing apoptosis and autophagy[J]. Jun-Qiang Zhang, Yu-Min Li, Tao Liu, Second Hospital of Lanzhou University, Lanzhou 730030, Gansu Province, China; Gansu Provincial Key Laboratory of Digestive System Tumors, Lanzhou 730030, Gansu Province, ChinaWen-Ting He, Xun Li, Wen-Ce Zhou, Department of General Surgery, First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, ChinaYing-Tai Chen, Xiao-Hui Chen, Jian-Feng Yi, Zhi-Jian Ren, First Clinical Medical School of Lanzhou University, Lanzhou 730000, Gansu Province, China. World Journal of Gastroenterology. 2010(34)
[10]苦参碱对腺样囊性癌细胞周期阻滞和端粒酶催化亚基表达的影响[J]. 赵军方,谢伟红,李新明,陈万涛,孙明磊,方政,孙强. 华西口腔医学杂志. 2010(03)
本文编号：3449847
【文章来源】：辽宁中医药大学辽宁省
【文章页数】：110 页
【学位级别】：博士
【部分图文】：
结肠癌细胞发生EMT改变
.氧化苦参碱分子结构（oxymatrinere 2. The molecular structure of oxy氧化苦参碱对 RKO 细胞增殖的抑制ect of oxymatrine on the proliferatio24 h 48 h 4.07±1.39 4.64±2.45 6.39±2.17 7.76±4.3 11.48±2.8118.22±5.18a28.91±1.1a38.22±3.86a46.75±5.23a51.05±5.67a55.51±2.6a63.34±7a69.74±3.19a74.63±3.92a85.88±3.59a87.74±3.02a组 (OM 0 mg/mL).
图 2.氧化苦参碱分子结构（oxymatrine，OM）Figure 2. The molecular structure of oxymatrine.表 1 氧化苦参碱对 RKO 细胞增殖的抑制率(%)Table 1. The inhibitory effect of oxymatrine on the proliferation inhibition of RKOM(mg/mL) 24 h 48 h 72 h0.125 4.07±1.39 4.64±2.45 5.46±1.320.25 6.39±2.17 7.76±4.3 11.54±6.120.5 11.48±2.8118.22±5.18a25.43±2.88a128.91±1.1a38.22±3.86a39.01±4.01a246.75±5.23a51.05±5.67a51.75±0.75a455.51±2.6a63.34±7a67.94±2.7a869.74±3.19a74.63±3.92a74.56±3.74a2085.88±3.59a87.74±3.02a90.33±2.28aaP < 0.05 vs. 对照组 (OM 0 mg/mL).
【参考文献】：
期刊论文
[1]氧化苦参碱抑制DBTC刺激的胰腺腺泡细胞中上皮间质转化相关蛋白及TβRⅡ和p-Smad2/3表达[J]. 张斌,许威,李如月,张青,向晓辉,夏时海. 遵义医学院学报. 2017(05)
[2]氧化苦参碱干预TGF-β1诱导A549细胞上皮-间质转化作用研究[J]. 刘蕾,马壮,谢华,孙文武. 陕西医学杂志. 2016(11)
[3]Effect of h GC-MSCs from human gastric cancer tissue on cell proliferation, invasion and epithelial-mesenchymal transition in tumor tissue of gastric cancer tumor-bearing mice[J]. Lin Song,Xin Zhou,Hong-Jun Jia,Mei Du,Jin-Ling Zhang,Liang Li. Asian Pacific Journal of Tropical Medicine. 2016(08)
[4]Dexamethasone inhibits hypoxia-induced epithelial-mesenchymal transition in colon cancer[J]. Jung Ho Kim,You-Jin Hwang,Sang Hoon Han,Young Eun Lee,Saerom Kim,Yoon Jae Kim,Jae Hee Cho,Kwang An Kwon,Ju Hyun Kim,Se-Hee Kim. World Journal of Gastroenterology. 2015(34)
[5]Epithelial-mesenchymal, mesenchymal-epithelial, and endothelial-mesenchymal transitions in malignant tumors: An update[J]. Simona Gurzu,Sabin Turdean,Attila Kovecsi,Anca Otilia Contac,Ioan Jung. World Journal of Clinical Cases. 2015(05)
[6]氧化苦参碱抑制高糖诱导的大鼠肾小管上皮-间充质转化及其机制研究[J]. 刘丽荣,李霜,王圆圆,石明隽,肖瑛,郭兵. 中国病理生理杂志. 2013(12)
[7]Oxymatrine liposome attenuates hepatic fibrosis via targeting hepatic stellate cells[J]. Ning-Li Chai,Hui Shi,Chang-Hao Cai,Jun Wan,Shi-Ping Xu,Ben-Yan Wu,Department of Gastroenterology,South Building of Chinese People’s Liberation Army General Hospital,Beijing 100853,China Qiang Fu,Department of Gastroenterology,Xi’an Children’s Hospital,Xi’an 710002,Shaanxi Province,China. World Journal of Gastroenterology. 2012(31)
[8]氧化苦参碱对人胃癌MGC-803细胞裸鼠皮下移植瘤形态学影响的作用[J]. 孙宁,徐玉芳,刘粉霞. 中医学报. 2010(06)
[9]Antitumor effect of matrine in human hepatoma G2 cells by inducing apoptosis and autophagy[J]. Jun-Qiang Zhang, Yu-Min Li, Tao Liu, Second Hospital of Lanzhou University, Lanzhou 730030, Gansu Province, China; Gansu Provincial Key Laboratory of Digestive System Tumors, Lanzhou 730030, Gansu Province, ChinaWen-Ting He, Xun Li, Wen-Ce Zhou, Department of General Surgery, First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, ChinaYing-Tai Chen, Xiao-Hui Chen, Jian-Feng Yi, Zhi-Jian Ren, First Clinical Medical School of Lanzhou University, Lanzhou 730000, Gansu Province, China. World Journal of Gastroenterology. 2010(34)
[10]苦参碱对腺样囊性癌细胞周期阻滞和端粒酶催化亚基表达的影响[J]. 赵军方,谢伟红,李新明,陈万涛,孙明磊,方政,孙强. 华西口腔医学杂志. 2010(03)
本文编号：3449847
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