甘草次酸修饰姜黄素阳离子脂质体对肿瘤Walker256细胞的影响
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摘要
目的:研究姜黄素及甘草次酸修饰姜黄素阳离子脂质体对Walker256细胞的影响。方法:不同浓度姜黄素与甘草次酸修饰姜黄素阳离子脂质体处理Walker256细胞后,采用CCK-8法检测细胞增殖抑制率;用流式细胞仪检测细胞吸收、细胞周期变化情况;Annexin V/PI双染法检测细胞凋亡;Western blot检测Wnt及β-catenin表达水平。结果:姜黄素和甘草次酸修饰姜黄素阳离子脂质体对肿瘤细胞Walker256均具有明显的抑制作用。与游离姜黄素相比,甘草次酸修饰姜黄素阳离子脂质体明显增强细胞对姜黄素的吸收,显著增强对Walker256细胞的增殖抑制、凋亡、细胞周期G2期的阻滞作用,明显下调Wnt及β-catenin的表达。结论:甘草次酸修饰姜黄素阳离子脂质体比游离姜黄素具有更强的抗肿瘤Walker256细胞的作用。
OBJECTIVE To study the inhibitory effect of glycyrrhetinic acid modified curcumin-loaded cationic liposomes(GAMCLCL) on Walker 256 cells. METHODS The CCK-8 method was used to test the proliferation inhibition rate of Walker 256 cells after treated with Curcumin(20, 10, 5, 2.50, and 1.25 μg·mL~(-1)), GAMCLCL(20, 10, 5, 2.50, and 1.25 μg·mL~(-1)) in corresponding concentration for different time points(24, 48 h). Flow cytometry was used to detect the cell adoption and the cell cycle of Walker 256 cells after treated with Curcumin(10 μg·mL~(-1)), GAMCLCL(10 μg·mL~(-1)) for 24 h. Annexin V/PI double staining method was used to detect the cell apoptosis. Western blot was adopted to detect the Wnt and β-catenin.RESULTS Curcumin, GAMCLCL had significant inhibitory effect on Walker 256 cells in a time-and concentration-dependent manner, Compared with free curcumin, the GAMCLCL significantly increased the cell adoption and enhanced the proliferation inhibition, the cell apoptosis, the G2 arrest, and substantially downregulated the expression of Wnt and β-catenin. CONCLUSION GAMCLCL has the more stronger antitumor effect against Walker 256 cells than that of free curcumin.
OBJECTIVE To study the inhibitory effect of glycyrrhetinic acid modified curcumin-loaded cationic liposomes(GAMCLCL) on Walker 256 cells. METHODS The CCK-8 method was used to test the proliferation inhibition rate of Walker 256 cells after treated with Curcumin(20, 10, 5, 2.50, and 1.25 μg·mL~(-1)), GAMCLCL(20, 10, 5, 2.50, and 1.25 μg·mL~(-1)) in corresponding concentration for different time points(24, 48 h). Flow cytometry was used to detect the cell adoption and the cell cycle of Walker 256 cells after treated with Curcumin(10 μg·mL~(-1)), GAMCLCL(10 μg·mL~(-1)) for 24 h. Annexin V/PI double staining method was used to detect the cell apoptosis. Western blot was adopted to detect the Wnt and β-catenin.RESULTS Curcumin, GAMCLCL had significant inhibitory effect on Walker 256 cells in a time-and concentration-dependent manner, Compared with free curcumin, the GAMCLCL significantly increased the cell adoption and enhanced the proliferation inhibition, the cell apoptosis, the G2 arrest, and substantially downregulated the expression of Wnt and β-catenin. CONCLUSION GAMCLCL has the more stronger antitumor effect against Walker 256 cells than that of free curcumin.
引文
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[4] Zhao BB,Li HM,Gao X,et al.The herbal compound “diwuyanggan” modulates liver regeneration by affecting the hepatic stem cell microenvironment in 2-acetylaminofluorene/partial hepatectomy rats[J].Evid Based Complement Alternat Med,2015:468303[PMID:25628749 DOI:10.1155/2015/468303]
[5] Li HM.Construction and application of tertiary prevention program for liver cancer based on “tonifying the kidney to promote liver regeneration” [J].Chin J Integr Trad Westen Med Liver Dis(中西医结合肝病杂志),2015,25(06):369-372.
[6] Li HM,Zhao BB,Gao X.Tonifying kidney to modulate liver regeneration microenviroment to prevent and cure liver cancer[J].J Hubei Univ Chin Med(湖北中医药大学学报),2015,17(01):5-8.
[7] Hanmin Li,Zhihua Ye,Jun Zhang,et al.Clinical trial with traditional Chinese medicine intervention ''tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment'' for chronic hepatitis B-associated liver failure[J].World J Gastroenterol,2014,20(48):18458-18465.
[8] Li H,Zhang L.Liver regeneration microenvironment of hepato-cellular carcinoma for prevention and therapy [J].Oncotarget,2017,8(1):1805-1813.
[9] Li Hanmin,Ye Zhihua.The Microenvironment of Liver Regeneration in Liver Cancer [J].Chin J Integr Med (中国中西医结合杂志),2017,23(7):555-560.
[10] Li HM.Chinese medicine regulates liver regeneration:Research progress and prospect[J].World Chin J Dig(世界华人消化杂志),2017,25(15):1338-1344.
[11] Zhou JJ,Zheng YC,Li MY,et al.Advances in pharmacological studies of curcumin[J].J Jilin Med Univ(吉林医药学院学报),2016,37(04):304-307.
[12] Zhang B,Ye LH.The research progress of curcumin anti-cancer mechanism [J].Acta Chin Med Pharm(中医药学报),2013,41(01):121-123.
[13] Wei JL,Deng SK.The research progress of curcumin antitumor mechanism [J].Hainan Med J(海南医学),2016,27(17):2828-2831.
[14] Li HM,Yan XS,Ming AP.The effect of liposome-curcumin on inhibitory Bel-7402 cell proliferation and induction apoptosis[J].Chin J Integr Trad Western Med Liver Dis(中西医结合肝病杂志),2005,15(4):214-217.
[15] Li HM,Yan XS,Ming AP,et al.Stability of anti-liver cancer efficacy by liposome-curcumin in water solution[J].Chin Trad Herbal Drugs(中草药),2006,37(04):561-565.
[16] Mingrong Cheng,Xiaoyan Gao,Yong Wang,et al.Synthesis of Glycyrrhetinic Acid-Modified Chitosan 5-Fluorouracil Nanoparticles and Its Inhibition of Liver Cancer Characteristics in Vitro and in Vivo[J].Mar Drugs,2013,11(9):3517-3536.
[17] Jingde Chen,Hong Jiang,Yin Wu,et al.A novel glycyrrhetinic acid-modified oxaliplatin liposome for liver-targeting and in vitroivo evaluation[J].Drug Des Devel Ther,2015,9:2265-2275.
[18] Wu C,Guo WY,Zhang L.Preparation of glycyrrhetic acid derivatives-modified norcantharidin liposome and study on its liver-targeting property in mice[J].China pharmacy(中国药房),2009,20(28):2184-2186.
[19] Yan DH,Yan LN.Several problems on the establishment of transplanted hepatic cancer models in SD rats[J].Chin J Bases Clin Gen Surg (中国普外基础与临床杂志),2003,10(02):128-130.
[20] Gu W,Shen J,Zhai XF.Preliminary study on biological behavior and staging of transplanted hepatoma in rats[J].J Chin Integr Med(中西医结合学报),2005,3 (02):136-138.
[21] Zheng Q,Xu HF.Research progress of Wnt/β-catenin signaling pathway in liver cancer[J].Int J Dig Dis(国际消化病杂志),2010,30(02):76-78.
[22] Deng W,Xiang Q,Li B.Study on the mechanism of sanqi plus huangqi on walker 256 liver metastasis in experimental rats[J].J Guangxi Med Uni(广西医科大学学报),2014,31(04):549-552.
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