苍耳亭抑制肝癌HepG2体内外药效研究
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摘要
目的通过体外肿瘤细胞抑制实验及体内抗肿瘤实验,探讨苍耳亭体内外抗人肝癌细胞Hep G2的作用。方法体内通过构建裸鼠肝癌自发转移模型,并随机分成空白对照组、苍耳亭低、高剂量组,连续腹腔注射2周,完整剥离肿瘤组织,称取瘤质量,计算抑瘤率,并且剥取主要脏器,计算脾指数与胸腺指数;体外通过MTT、Transwell实验初步观察苍耳亭对癌细胞侵袭迁移的作用。结果体内实验结果显示苍耳亭低剂量组与高剂量组的抑瘤率分别为17.61%和39.57%,具有较好的抑制肿瘤活性(P<0.05,P<0.01),并且高低剂量组间比较差异有统计学意义(P<0.05)。体外苍耳亭抑制Hep G2细胞增殖效果明显,与空白对照组DMSO比较,16μM时诱导肿瘤细胞凋亡差异有统计学意义(P<0.01),其IC50值为29.04μM。同时,Transwell实验显示也能抑制体外癌细胞侵袭。结论苍耳亭体内外对肝癌Hep G2细胞均具有较强的抑制作用,具有浓度依赖性。
Objective To explore the anticancer effect of xanthium in vitro and in vivo in Hep G2 of hepatocellular carcinoma through the in vitro experiment of carcinoma cell inhibition.Methods The models of spontaneous metastasis of hepatocelular carcinoma were established in naked mice and they were randomized into a blank control group,a low-dose xanthatin group and a high-dose xanthatin group.The intraperitoneal injection was given continuously for 2 weeks.The tumor tissue was exfoliated completed,and thus tumor mass was weighted and the tumor inhibition was calculated.The main organs were separated and the spleen index and thymus index were calculated.In vitro,with MTT and Transwell experiments,the effect of xanthatin on cellular invasion and migration was observed.Results The in vivo experiment results indicated that the tumor inhibition rates in the low-dose xanthatin group and the high-dose group were 17.61% and 39.57% respectively,presenting the satisfactory activity of tumor inhibition(P<0.05,P<0.01).The inhibition rate was different significantly between the high-dose group and the low-dose group(P<0.05).The in vitro experiment presented the remarkable effect of the inhibition of Hep G2 proliferation.In DMSO comparison with the blank control group,the difference in the induced tumor cell apoptosis was significant at 16 μM(P<0.01) and IC50 value was 29.04 μM.At the same time,the inhibition in vitro of cancer cell invasion was also presented in Transwell experiment.Conclusion Xanthatin presents the strong inhibition of Hep G2 of hepatoceluar carcinoma in vitro and in vivo and the concentration dependence.
Objective To explore the anticancer effect of xanthium in vitro and in vivo in Hep G2 of hepatocellular carcinoma through the in vitro experiment of carcinoma cell inhibition.Methods The models of spontaneous metastasis of hepatocelular carcinoma were established in naked mice and they were randomized into a blank control group,a low-dose xanthatin group and a high-dose xanthatin group.The intraperitoneal injection was given continuously for 2 weeks.The tumor tissue was exfoliated completed,and thus tumor mass was weighted and the tumor inhibition was calculated.The main organs were separated and the spleen index and thymus index were calculated.In vitro,with MTT and Transwell experiments,the effect of xanthatin on cellular invasion and migration was observed.Results The in vivo experiment results indicated that the tumor inhibition rates in the low-dose xanthatin group and the high-dose group were 17.61% and 39.57% respectively,presenting the satisfactory activity of tumor inhibition(P<0.05,P<0.01).The inhibition rate was different significantly between the high-dose group and the low-dose group(P<0.05).The in vitro experiment presented the remarkable effect of the inhibition of Hep G2 proliferation.In DMSO comparison with the blank control group,the difference in the induced tumor cell apoptosis was significant at 16 μM(P<0.01) and IC50 value was 29.04 μM.At the same time,the inhibition in vitro of cancer cell invasion was also presented in Transwell experiment.Conclusion Xanthatin presents the strong inhibition of Hep G2 of hepatoceluar carcinoma in vitro and in vivo and the concentration dependence.
引文
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[9]Zhang lei,Tao li,Ruanjunshan,et al. Xanthatin Induces G2/M Cell Cycle Arrest and Apoptosis in Human Gastric Carcinoma MKN-45Cells[J]. Planta Medica,2012,78(9):890-895.
[10]Li Wei-dong,Wu Yu,Zhang lei,et al. Characterization of Xanthatin:Anticancer properties and mechanisms of inhibited murine melanoma in vitro and in vivo[J]. Phytomedicine,2013(20):865-873.
[11]Li Tao,Xiao Bosheng,Lei Zhang,et al. Xanthatin anti-tumor cytotoxicity is mediated via glycogen synthase kinase-3βandβ-catenin[J]. Biochem Pharmacol,2016(115):18-27.
[12]RojasRojas T,Bourdy G,Ruiz E,et al. Herbal Medicine Practices of Patients With Liver Cancer in Peru[J]. Integr Cancer Ther,2016,3(3):211.
[13]Romero M,Zanuy M. Rosell E,Cascante M,et al. Optimization of Xanthatin extraction from Xanthium spinosum L. and its cytotoxic,anti-angiogenesis and antiviral properties[J]. Eur J Med Chem,2015(90):491-496.
[2]Llovet JM,Burroughs A,Bruix J. Hepatocellular carcinoma[J]. Lancet,2003,362(9399):1907-1917.
[3]Pang RW,Joh JW,Johnson PJ,et al. Biology of hepatocellular Carcinoma[J]. Ann Surg Oncol,2008,15(4):962-971.
[4]Yang LY,Fang F,Ou DP,et al. Solitary large hepatocellular carcinoma:a specific subtype of hepatocellular carcinoma with good outcome after hepatic resection[J]. Ann Surg,2009,249(1):118-123.
[5]Kim YS,Kim JS,Park SH,et al. Two Cytotoxic Sesquiterpene Lactones from the Leaves of Xanthium strumarium and their in vitro Inhibitory Activity on Farnesyltransferase[J]. Planta Med,2003,69:375-377.
[6]Ramíre-Erosa I,Huang Y,Hickie RA,et al. Xanthatin and xanthinosin from the burs of Xanthium strumarium L. as potential anticancer agents[J]. Can J Physiol Pharmacol,2007(85):1160-1172.
[7]Kim In-Tae,Park-Young-Mi,Won JH,et al. Methanol Extract of Xanthium strumarium L. Possesses Antiinflammatory and Anti-nociceptive Activitie[J]. Bio Pharm Bull,2005,28(1):94-100.
[8]Zhang lei,Ruan junshan,Yan linggen,et al. Xanthatin induces cell cycle arrest at G2/M checkpoint and apoptosis via disrupting NFkappaB pathway in A549 non-small-cell lung cancer cells[J].Molecules,2012,17(4):3736-3750.
[9]Zhang lei,Tao li,Ruanjunshan,et al. Xanthatin Induces G2/M Cell Cycle Arrest and Apoptosis in Human Gastric Carcinoma MKN-45Cells[J]. Planta Medica,2012,78(9):890-895.
[10]Li Wei-dong,Wu Yu,Zhang lei,et al. Characterization of Xanthatin:Anticancer properties and mechanisms of inhibited murine melanoma in vitro and in vivo[J]. Phytomedicine,2013(20):865-873.
[11]Li Tao,Xiao Bosheng,Lei Zhang,et al. Xanthatin anti-tumor cytotoxicity is mediated via glycogen synthase kinase-3βandβ-catenin[J]. Biochem Pharmacol,2016(115):18-27.
[12]RojasRojas T,Bourdy G,Ruiz E,et al. Herbal Medicine Practices of Patients With Liver Cancer in Peru[J]. Integr Cancer Ther,2016,3(3):211.
[13]Romero M,Zanuy M. Rosell E,Cascante M,et al. Optimization of Xanthatin extraction from Xanthium spinosum L. and its cytotoxic,anti-angiogenesis and antiviral properties[J]. Eur J Med Chem,2015(90):491-496.