大黄素-8-O-β-D-葡萄糖苷体内外抗肝癌活性研究
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摘要
目的:研究大黄素-8-O-β-D-葡萄糖苷(EG)对人肝癌细胞系HepG2和荷肝癌H22移植瘤小鼠肿瘤的影响。方法:EG 50,100,200和400μg·m L-1作用于人肝癌HepG2细胞后,MTT法检测细胞活力;采用CFSE荧光染色结合流式细胞术测定细胞分裂增殖情况;EG低(1 mg·kg-1)、高(5 mg·kg-1)剂量作用于荷肝癌H22移植瘤小鼠,另设对照组和5-Fu阳性药组,给药13 d后计算抑瘤率和脏器指数。结果:EG呈剂量和时间依赖性抑制HepG2的细胞活力,EG作用HepG2细胞48和72 h的IC50分别为331.27和224.36μg·m L-1;流式细胞术结果表明,EG作用后HepG2细胞分裂增殖能力受到明显抑制;低、高剂量EG对荷肝癌H22移植瘤小鼠的抑瘤率分别为26.34%和58.83%(P<0.05),对脾脏指数和胸腺指数没有明显影响。结论:EG在体内外均具有抗肝癌活性,EG对人肝癌细胞HepG2细胞活力具有明显的抑制作用,其机制与抑制细胞分裂增殖能力有关;EG对荷肝癌H22移植瘤小鼠肿瘤具有显著抑制作用,且对小鼠免疫器官没有明显影响。
Objective: To investigate the antitumor activity of emodin-8-O-β-D-glucopyranoside( EG) on human hepatocellular carcinoma cell line HepG2 and hepatic carcinoma H22 tumor-bearing mice. Methods: Cell viabilities were detected by MTT assay after being treated with EG of 50,100,200 and 400 μg·mL~(-1). Cell proliferation was determined by flow cytometry with CFSE fluorescent dye staining. H22 tumor-bearing mice were divided into control group,EG low dose( 1 mg·kg~(-1)) group,EG high dose( 5 mg·kg~(-1)) group and 5-Fu group.The tumor inhibition rate,spleen index and thymus index were calculated after 13 days of treatment. Results: EG inhibited the cell viability of HepG2 in a dose-and time-dependent manner. The IC50 values of EG on HepG2 cells were 331. 27 μg·mL~(-1) and 224. 36 μg·mL~(-1) at 48 h and 72 h respectively. The results of flow cytometry showed that the proliferation of HepG2 cells was significantly inhibited by EG. The tumor inhibitory rates of EG in low and high dose groups were 26. 34% and 58. 83%( P < 0. 05),respectively,and EG had no significant effect on spleen index and thymus index in H22 tumor-bearing mice. Conclusion: EG had anti-hepatocarcinoma activity both in vivo and in vitro. EG had obvious inhibitory effect on cell viability in HepG2 cells,which was proved to be relatedto its inhibiting ability on the proliferation of tumor cells. The H22 tumor growth in tumor-bearing mice was inhibited by EG and no obvious changes were detected in spleen and thymus index.
Objective: To investigate the antitumor activity of emodin-8-O-β-D-glucopyranoside( EG) on human hepatocellular carcinoma cell line HepG2 and hepatic carcinoma H22 tumor-bearing mice. Methods: Cell viabilities were detected by MTT assay after being treated with EG of 50,100,200 and 400 μg·mL~(-1). Cell proliferation was determined by flow cytometry with CFSE fluorescent dye staining. H22 tumor-bearing mice were divided into control group,EG low dose( 1 mg·kg~(-1)) group,EG high dose( 5 mg·kg~(-1)) group and 5-Fu group.The tumor inhibition rate,spleen index and thymus index were calculated after 13 days of treatment. Results: EG inhibited the cell viability of HepG2 in a dose-and time-dependent manner. The IC50 values of EG on HepG2 cells were 331. 27 μg·mL~(-1) and 224. 36 μg·mL~(-1) at 48 h and 72 h respectively. The results of flow cytometry showed that the proliferation of HepG2 cells was significantly inhibited by EG. The tumor inhibitory rates of EG in low and high dose groups were 26. 34% and 58. 83%( P < 0. 05),respectively,and EG had no significant effect on spleen index and thymus index in H22 tumor-bearing mice. Conclusion: EG had anti-hepatocarcinoma activity both in vivo and in vitro. EG had obvious inhibitory effect on cell viability in HepG2 cells,which was proved to be relatedto its inhibiting ability on the proliferation of tumor cells. The H22 tumor growth in tumor-bearing mice was inhibited by EG and no obvious changes were detected in spleen and thymus index.
引文
[1]李凯明,孙震晓.我国含大黄素-8-O-β-D-葡萄糖苷的植物资源整理[J].中国新药杂志,2016,25(24):2787-2792.
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[7]刘素华.大黄素-8-O-β-D-葡萄糖苷对人卵巢癌细胞系SKOV3细胞凋亡及Bcl-2表达的影响[J].中华医学杂志,2015,95(43):3541-3544.
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[10]陈静,冯光远,李登科,等.藏药余甘子鞣质部位对人肿瘤细胞凋亡与周期的影响[J].中国药物警戒,2016,13(4):193-196.
[11]LI ZM,WANG M,XU ZL,et al.Different cytotoxic effects of hydroxycamptothecin on human lung cancer cells and human embryo lung fibroblast cells[J].Chin J Pharmacol Toxicol,2014,28(3):315-320.
[12]孟艳秋,张伟晨,宁梓廷,等.积雪草酸A环开环衍生物的合成及体外抗肿瘤活性研究[J].中国新药杂志,2017,26(10):1157-1162.
[13]FERREIRA AK,PASQUALOTO KF,KRUYT FA,et al.BFD-22 a new potential inhibitor of BRAF inhibits the metastasis of B16F10 melanoma cells and simultaneously increased the tumor immunogenicity[J].Toxicol Appl Pharm,2016,295:56-67.
[14]冯光远,李登科,吴玲芳,等.藏药余甘子鞣质部位对小鼠移植性肿瘤的抑制作用[J].中国药物警戒,2015,12(4):193-196.
[15]GUO X,YANG Z,WANG J,et al.Synergistic antitumor effect of puerarin combined with 5-fluorouracil on gastric carcinoma[J].Mol Med Rep,2015,11(4):2562-2568.
[16]金光明,尹学哲,金明姬,等.聚乙二醇化多西他赛白蛋白纳米粒用于非小细胞肺癌模型的实验研究[J].中国新药杂志,2017,26(23):2871-2876.
[17]NAGARAJU GP,ALESE OB,LANDRY J,et al.HSP90 inhibition downregulates thymidylate synthase and sensitizes colorectal cancer cell lines to the effect of 5FU-based chemotherapy[J].Oncotarget,2014,5(20):9980-9991.
[18]孙震晓.大黄素-8-O-β-D-葡萄糖苷的抗肿瘤活性及其新用途:中国,CN103191140A[P].2013-08-07.
[2]WANG C,ZHANG D,MA H,et al.Neuroprotective effects of emodin-8-O-β-D-glucoside in vivo and in vitro[J].Eur J Pharmacol,2007,577(1):58-63.
[3]陈万生,徐江平,李力,等.大黄素-8-O-β-D-吡喃葡萄糖苷的促智活性及其机制[J].中草药,2001,32(1):39-41.
[4]汲广全,杨娟,杨小生.夜交藤改善睡眠活性成分研究[J].中成药,2011,33(3):514-516.
[5]李登科.何首乌大黄素-8-O-β-D-葡萄糖苷的抗肿瘤作用研究[D].北京:北京中医药大学,2015.
[6]李宝赛.何首乌抗肝癌活性成分分离与机制初探[D].北京:北京中医药大学,2013.
[7]刘素华.大黄素-8-O-β-D-葡萄糖苷对人卵巢癌细胞系SKOV3细胞凋亡及Bcl-2表达的影响[J].中华医学杂志,2015,95(43):3541-3544.
[8]王征.大黄素-8-O-β-D-葡萄糖苷多晶型研究及其对药效学和药动学的影响[D].北京:第二军医大学,2002.
[9]李登科,李宝赛,崔宝弟,等.何首乌中大黄素-8-O-β-D-葡萄糖苷的分离纯化与体外抗癌活性研究[J].癌变畸变突变,2014,26(6):401-407.
[10]陈静,冯光远,李登科,等.藏药余甘子鞣质部位对人肿瘤细胞凋亡与周期的影响[J].中国药物警戒,2016,13(4):193-196.
[11]LI ZM,WANG M,XU ZL,et al.Different cytotoxic effects of hydroxycamptothecin on human lung cancer cells and human embryo lung fibroblast cells[J].Chin J Pharmacol Toxicol,2014,28(3):315-320.
[12]孟艳秋,张伟晨,宁梓廷,等.积雪草酸A环开环衍生物的合成及体外抗肿瘤活性研究[J].中国新药杂志,2017,26(10):1157-1162.
[13]FERREIRA AK,PASQUALOTO KF,KRUYT FA,et al.BFD-22 a new potential inhibitor of BRAF inhibits the metastasis of B16F10 melanoma cells and simultaneously increased the tumor immunogenicity[J].Toxicol Appl Pharm,2016,295:56-67.
[14]冯光远,李登科,吴玲芳,等.藏药余甘子鞣质部位对小鼠移植性肿瘤的抑制作用[J].中国药物警戒,2015,12(4):193-196.
[15]GUO X,YANG Z,WANG J,et al.Synergistic antitumor effect of puerarin combined with 5-fluorouracil on gastric carcinoma[J].Mol Med Rep,2015,11(4):2562-2568.
[16]金光明,尹学哲,金明姬,等.聚乙二醇化多西他赛白蛋白纳米粒用于非小细胞肺癌模型的实验研究[J].中国新药杂志,2017,26(23):2871-2876.
[17]NAGARAJU GP,ALESE OB,LANDRY J,et al.HSP90 inhibition downregulates thymidylate synthase and sensitizes colorectal cancer cell lines to the effect of 5FU-based chemotherapy[J].Oncotarget,2014,5(20):9980-9991.
[18]孙震晓.大黄素-8-O-β-D-葡萄糖苷的抗肿瘤活性及其新用途:中国,CN103191140A[P].2013-08-07.
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