獐牙菜苦苷对MGC803细胞的体内外抑制作用
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摘要
背景:胃癌是最常见的恶性肿瘤之一,抑制胃癌细胞增殖是抗癌药物研发的关键。目的:研究獐牙菜苦苷在体内外对MGC803细胞增殖的影响。方法:MGC803细胞予以不同浓度獐牙菜苦苷(0、30、60、90μg/mL)培养48h,以MTT法检测细胞活性,Annexin V-FITC/PI法检测细胞凋亡率,ELISA法检测Bax、Bcl-2含量。建立BALB/c裸鼠MGC803移植瘤模型,尾静脉注射不同浓度獐牙菜苦苷(0、40、60、80mg/kg),肿瘤体积长至1000mm~3时处死裸鼠,记录裸鼠开始和最终的体质量,以免疫组化法检测Ki-67蛋白表达。结果:与对照组相比,不同浓度獐牙菜苦苷可有效抑制MGC803细胞增殖,诱导细胞凋亡,Bax含量明显升高,Bcl-2含量明显降低(P<0.05)。在MGC803细胞裸鼠移植瘤模型中,不同浓度獐牙菜苦苷组的肿瘤体积较对照组明显缩小(P<0.05),Ki-67蛋白表达明显减少(P<0.05)。结论:獐牙菜苦苷是一种安全有效的抗胃癌的植物单体。
Background: Gastric cancer is one of the most commonly seen malignant tumors. Inhibiting the proliferation of gastric cancer cells is the key for the development of anticancer drugs. Aims: To investigate the effect of swertiamarin on proliferation of MGC803 cells in vitro and in vivo. Methods: MGC803 cells were cultured with different concentrations of swertiamarin(0,30,60 and 90 μg/m L) for 48 hours. The cell activity were detected by MTT. The apoptosis rate was measured by Annexin V-FITC/PI assay. The contents of Bax and Bcl-2 were detected by ELISA. MGC803 cell xenograft tumor in BALB/c nude mice was established,and different concentrations of swertiamarin(0,40,60 and 80 mg/kg) were injected through caudal vein. Nude mice were killed when the volume of tumor was 1000 mm~3. The initial and final body weights of nude mice were recorded. The protein expression of Ki-67 was detected by immunohistochemistry. Results:Compared with control group,different concentrations of swertiamarin effectively inhibited the proliferation of MGC803 cells,induced cell apoptosis,increased the content of Bax,while the content of Bcl-2 was significantly decreased(P<0.05). In BALB/c nude mice with MGC803 cell xenograft tumor,the volume of tumor,protein expression of Ki-67 decreased significantly in groups injected with different concentrations of swertiamarin than in control group(P<0.05).Conclusions: Swertiamarin is a safe and effective anti-gastric tumor plant agent.
Background: Gastric cancer is one of the most commonly seen malignant tumors. Inhibiting the proliferation of gastric cancer cells is the key for the development of anticancer drugs. Aims: To investigate the effect of swertiamarin on proliferation of MGC803 cells in vitro and in vivo. Methods: MGC803 cells were cultured with different concentrations of swertiamarin(0,30,60 and 90 μg/m L) for 48 hours. The cell activity were detected by MTT. The apoptosis rate was measured by Annexin V-FITC/PI assay. The contents of Bax and Bcl-2 were detected by ELISA. MGC803 cell xenograft tumor in BALB/c nude mice was established,and different concentrations of swertiamarin(0,40,60 and 80 mg/kg) were injected through caudal vein. Nude mice were killed when the volume of tumor was 1000 mm~3. The initial and final body weights of nude mice were recorded. The protein expression of Ki-67 was detected by immunohistochemistry. Results:Compared with control group,different concentrations of swertiamarin effectively inhibited the proliferation of MGC803 cells,induced cell apoptosis,increased the content of Bax,while the content of Bcl-2 was significantly decreased(P<0.05). In BALB/c nude mice with MGC803 cell xenograft tumor,the volume of tumor,protein expression of Ki-67 decreased significantly in groups injected with different concentrations of swertiamarin than in control group(P<0.05).Conclusions: Swertiamarin is a safe and effective anti-gastric tumor plant agent.
引文
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4 王薛,陈卓,向光芳. UPLC-Q-TOFMS法分析中药龙胆和秦艽的化学成分[J].解放军药学学报,2018,34(1):43-47.
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7 刘征辉,徐石勇,赵琳琳,等.金银花中抗炎活性成分獐牙菜苷和獐牙菜苦苷定量方法的研究[J].中国现代中药,2016,18(3):321-325.
8 周源,刘英姿,李锋,等.獐芽菜苦苷对乙醇致小鼠胃溃疡的保护作用[J].中国新药杂志,2008,17(20):1768-1769,1779.
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10 赵李剑,左泽乘,邹洪波,等.川东獐牙菜苦甙类成分的提取及其体外抗肿瘤作用研究[J].中医药导报,2006,12(5):62-64.
11 李润琴,杨建平,黄春,等.川东獐牙菜提取物抑制体外人肝癌细胞的生长[J].中药药理与临床,2011,27(2):90-93.
12 Lee JS,Jung WK,Jeong MH,et al. Sanguinarine induces apoptosis of HT-29 human colon cancer cells via the regulation of Bax/Bcl-2 ratio and caspase-9-dependent pathway[J]. Int J Toxicol,2012,31(1):70-77.
13 Li H,Lv B,Kong L,et al. Nova1 mediates resistance of rat pheochromocytoma cells to hypoxia-induced apoptosis via the Bax/Bcl-2/caspase-3 pathway[J]. Int J Mol Med,2017,40(4):1125-1133.
14 贾振军,郭雪洁,苗新东,等. p16、p53、Cerb B2和ki-67在胃癌及癌前病变中的表达及意义[J].中国现代普通外科进展,2014,17(8):611-615.
2 Rosania R,Varbanova M,Wex T,et al. Regulation of apoptosis is impaired in atrophic gastritis associated with gastric cancer[J]. BMC Gastroenterol, 2017, 17(1):84.
3 王丽,陈芬,符德欢,等.小儿腹痛草中獐牙菜苦苷与龙胆苦苷的含量测定[J].中国民族民间医药,2017,26(2):35-37.
4 王薛,陈卓,向光芳. UPLC-Q-TOFMS法分析中药龙胆和秦艽的化学成分[J].解放军药学学报,2018,34(1):43-47.
5 高瑞锡,梅枝意,黄先菊,等.黄秦艽根化学成分研究[J].中草药,2018,49(3):521-529.
6 杨红霞,李岑,毕宏涛,等.藏药印度獐牙菜提取物红外光谱分析及保肝活性比较研究[J].天然产物研究与开发,2018,30(4):668-675.
7 刘征辉,徐石勇,赵琳琳,等.金银花中抗炎活性成分獐牙菜苷和獐牙菜苦苷定量方法的研究[J].中国现代中药,2016,18(3):321-325.
8 周源,刘英姿,李锋,等.獐芽菜苦苷对乙醇致小鼠胃溃疡的保护作用[J].中国新药杂志,2008,17(20):1768-1769,1779.
9 李尚秀,汪婷,田倩,等.西南獐牙菜化学成分及其抗前列腺增生活性[J].中国药学杂志,2015,50(6):502-506.
10 赵李剑,左泽乘,邹洪波,等.川东獐牙菜苦甙类成分的提取及其体外抗肿瘤作用研究[J].中医药导报,2006,12(5):62-64.
11 李润琴,杨建平,黄春,等.川东獐牙菜提取物抑制体外人肝癌细胞的生长[J].中药药理与临床,2011,27(2):90-93.
12 Lee JS,Jung WK,Jeong MH,et al. Sanguinarine induces apoptosis of HT-29 human colon cancer cells via the regulation of Bax/Bcl-2 ratio and caspase-9-dependent pathway[J]. Int J Toxicol,2012,31(1):70-77.
13 Li H,Lv B,Kong L,et al. Nova1 mediates resistance of rat pheochromocytoma cells to hypoxia-induced apoptosis via the Bax/Bcl-2/caspase-3 pathway[J]. Int J Mol Med,2017,40(4):1125-1133.
14 贾振军,郭雪洁,苗新东,等. p16、p53、Cerb B2和ki-67在胃癌及癌前病变中的表达及意义[J].中国现代普通外科进展,2014,17(8):611-615.