多孔淀粉负载青蒿素微球的抗肿瘤活性研究
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摘要
探讨多孔淀粉负载青蒿素微球(ART-PS)与青蒿素原药(ART)在不同浓度下的抗肿瘤活性,以及分别联合全铁转铁蛋白后对肿瘤细胞的生长抑制作用。在体外实验中,取对数生长期的人肝癌细胞和正常肝细胞接种于96孔板中,不同浓度(0、50、100、150、200μmol·L~(-1))给药处理24h后,用MTT法分别检测多孔淀粉负载青蒿素微球与青蒿素原药对细胞的生长抑制作用。MTT结果显示,同等处理浓度下,多孔淀粉负载青蒿素微球对肿瘤细胞Hep G2和SMMC-7721的抑制效果都高于青蒿素原药,但与盐酸阿霉素相比,都具有较低的细胞毒性,对正常细胞HL7702的毒副作用非常低,结果与分别联合全铁转铁蛋白后对肿瘤细胞的生长抑制作用一致。多孔淀粉负载青蒿素微球对人肝癌细胞的增殖有明显的抑制作用,效果优于青蒿素原药,并对正常肝细胞的毒副作用非常低,为青蒿素在治疗癌症的应用与研究提供了重要的参考依据。
To investigate the antitumor activity of porous starch loaded artemisinin microspheres( ART-PS) and artemisinin active drugs( ART) at different concentrations,and the growth inhibition of tumor cells after combined with total ferritin,respectively,in the in vitro experiments,human hepatocellular carcinoma cells and normal hepatocytes at logarithmic growth stage were inoculated to 96-well plates at different contents( 0,50,100,150 and 200 μmol · L~(-1)). Concentrations determined by MTT,according to the results of equal treatment,porous starch load on tumor cell HepG2 artemisinin microspheres and the inhibition effect of SMMC-7721 were higher than that of artemisinin technical,but compared with doxorubicin hydrochloride,has low cytotoxicity,on the side effects of normal cells HL7702 is very low,the results associated with respectively after full iron transferrin inhibition for the growth of tumor cells. The porous starch loaded artemisinin microspheres had obvious inhibitory effect on the proliferation of human hepatocellular carcinoma cells,the effect was better than the original artemisinin drugs,and the toxic and side effects on normal hepatocytes were very low,it provides an important reference for the application and research of artemisinin in the treatment of cancer.
To investigate the antitumor activity of porous starch loaded artemisinin microspheres( ART-PS) and artemisinin active drugs( ART) at different concentrations,and the growth inhibition of tumor cells after combined with total ferritin,respectively,in the in vitro experiments,human hepatocellular carcinoma cells and normal hepatocytes at logarithmic growth stage were inoculated to 96-well plates at different contents( 0,50,100,150 and 200 μmol · L~(-1)). Concentrations determined by MTT,according to the results of equal treatment,porous starch load on tumor cell HepG2 artemisinin microspheres and the inhibition effect of SMMC-7721 were higher than that of artemisinin technical,but compared with doxorubicin hydrochloride,has low cytotoxicity,on the side effects of normal cells HL7702 is very low,the results associated with respectively after full iron transferrin inhibition for the growth of tumor cells. The porous starch loaded artemisinin microspheres had obvious inhibitory effect on the proliferation of human hepatocellular carcinoma cells,the effect was better than the original artemisinin drugs,and the toxic and side effects on normal hepatocytes were very low,it provides an important reference for the application and research of artemisinin in the treatment of cancer.
引文
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20.Meer T A,Moravkar K,Pawar J,et al.Crosslinked porous starch particles-a promising carrier[J].Polimery W Medycynie,2015,45(1):11-19.
21.Glenn G M,Klamczynski A P,Woods D F,et al.Encapsulation of plant oils in porous starch microspheres[J].Journal of Agricultural and Food Chemistry,2010,58(7):4180-4184.
22.Jiang T Y,Wu C,Cao Y K,et al.Preparation of novel porous starch microsphere foam for loading and release of poorly water soluble drug[J].Drug Development and Industrial Pharmacy,2014,40(2):252-259.
23.Ali M T,Fule R,Sav A,et al.Porous starch:a novel carrier for solubility enhancement of carbamazepine[J].AAPSPharm Sci Tech,2013,14(3):919-926.
24.Gao F,Li D,Bi C H,et al.The adsorption and release characteristics of CPFX in porous starch produced through different drying methods[J].Drying Technology,2013,31(13-14):1592-1599.
25.唐宜轩,韩丽,张定堃,等.多孔淀粉的制备及其在医药应用中的研究进展[J].中成药,2015,37(6):1321-1324.Tang Y X,Han L,Zhang D K,et al.Preparation of porous starch and its application in medicine[J].Chinese Traditional Patent Medicine,2015,37(6):1321-1324.
26.Ali M T,Fule R,SAV A,et al.Porous starch:a novel carrier for solubility enhancement of carbamazepine[J].AAPSPharm Sci Tech,2013,14(3):919-926.
27.Zhang Z W,Huang J,Jiang S J,et al.Porous starch based self-assembled nano-delivery system improves the oral absorption of lipophilic drug[J].International Journal of Pharmaceutics,2013,444(1-2):162-168.
28.Deng X R,Liu Z X,Liu F,et al.Holotransferrin enhances selective anticancer activity of artemisinin against human hepatocellular carcinoma cells[J].Journal of Huazhong U-niversity of Science and Technology[Medical Sciences],2013,33(6):862-865.
2.Tu Y Y.The discovery of artemisinin(qinghaosu)and gifts from Chinese medicine[J].Nature Medicine,2011,17(10):1217-1220.
3.Klayman D L.Qinghaosu(artemisinin):an antimalarial drug from China[J].Science,1985,228(4703):1049-1055.
4.Rosenthal P J,Meshnick S R.Hemoglobin catabolism and iron utilization by malaria parasites[J].Molecular and Biochemical Parasitology,1996,83(2):131-139.
5.Li Y.Qinghaosu(artemisinin):chemistry and pharmacology[J].Acta Pharmacologica Sinica,2012,33(9):1141-1146.
6.Firestone G L,Sundar S N.Anticancer activities of artemisinin and its bioactive derivatives[J].Expert Reviews in Molecular Medicine,2009,11:e32.
7.Efferth T,Dunstan H,Sauerbrey A,et al.The anti-malarial artesunate is also active against cancer[J].International Journal of Oncology,2001,18(4):767-773.
8.Efferth T,Sauerbrey A,Olbrich A,et al.Molecular modes of action of artesunate in tumor cell lines[J].Molecula Pharmacology,2003,64(2):382-394.
9.Tan W F,Feng S,Luo X J,et al.Artemisinin inhibits in vitro and in vivo invasion and metastasis of human hepatocellular carcinoma cells[J].Phytomedicine,2011,18(2-3):158-162.
10.Chaijaroenkul W,Viyanant,Mahavorasirikul W,et al.Cytotoxic activity of artemisinin derivatives against cholangiocarcinoma(CL-6)and hepatocarcinoma(Hep-G2)cell Lines[J].Asian Pacific Journal of Cancer Prevention,2011,12(1):55-59.
11.Hou J M,Wang D S,Zhang E W,et al.Experimental therapy of hepatoma with artemisinin and its derivatives:in vitro and in vivo activity,chemosensitization,and mechanisms of action[J].Clinical Cancer Research,2008,14(17):5519-5530.
12.Aquino I,Tsuboy M S F,Marcarini J C,et al.Genotoxic evaluation of the antimalarial drugs artemisinin and artesunate in human Hep G2 cells and effects on CASP3 and SOD1 gene expressions[J].Genetics and Molecular Research,2013,12(3):2517-2527.
13.郭彬,刘殿星,李雷雷,等.青蒿素调控P53蛋白诱导肝癌细胞凋亡的机制研究[J].标记免疫分析与临床,2017,24(3):314-316,325.Guo B,Liu D X,Li L L,et al.Study on the mechanism of artemisinin regulating P53 protein to induce apoptosis in hepatocellular carcinoma cells[J].Labeled Immunoassays and Clinical Medicine,2017,24(3):314-316,325.
14.李亚巍,张巍,李妍,等.青蒿素通过线粒体途径诱导人肝癌细胞Hep G2凋亡的分子机制研究[J].毒理学杂志,2018,32(3):194-198.Li Y W,Zhang W,Li Y,et al.Study on the molecular mechanism of artemisinin inducing Hep G2 apoptosis in human hepatocellular carcinoma cells through mitochondrial pathway[J].Journal of Toxicology,2018,32(3):194-198.
15.吴景华,郭佳培,曹青,等.青蒿素通过抑制IL-17/IL-17R表达诱导肝癌细胞凋亡的机制研究[J].现代预防医学,2017,44(4):697-700.Wu J H,Guo J P,Cao Q,et al.Study on the mechanism of artemisinin inducing apoptosis of liver cancer cells by inhibiting IL-17/IL-17R expression[J].Modern Preventive Medicine,2017,44(4):697-700.
16.朱文赫,陈丽红,许娜,等.双氢青蒿素诱导人肝癌细胞SMMC-7721凋亡及其分子机制研究[J].中国药学杂志,2018,53(3):187-192.Zhu W H,Chen L H,Xu N,et al.Apoptosis of human hepatocellular carcinoma cell SMMC-7721 induced by dihydroartemisininand its molecular mechanism[J].Chinese Journal of Pharmacy,2018,53(3):187-192.
17.Van Nijlen T,Brennan K,Van Den Mooter G,et al.Improvement of the dissolution rate of artemisinin by means of supercritical fluid technology and solid dispersions[J].International Journal of Pharmaceutics,2003,254(2):173-181.
18.Shahzad Y,Sohail S,Arshad M S,et al.Development of solid dispersions of artemisinin for transdermal delivery[J].International Journal of Pharmaceutics,2013,457(1):197-205.
19.Isacchi B,Arrigucci S,La Marca G,et al.Conventional and long-circulating liposomes of artemisinin:preparation,characterization,and pharmacokinetic profile in mice[J].Journal of Liposome Research,2011,21(3):237-244.
20.Meer T A,Moravkar K,Pawar J,et al.Crosslinked porous starch particles-a promising carrier[J].Polimery W Medycynie,2015,45(1):11-19.
21.Glenn G M,Klamczynski A P,Woods D F,et al.Encapsulation of plant oils in porous starch microspheres[J].Journal of Agricultural and Food Chemistry,2010,58(7):4180-4184.
22.Jiang T Y,Wu C,Cao Y K,et al.Preparation of novel porous starch microsphere foam for loading and release of poorly water soluble drug[J].Drug Development and Industrial Pharmacy,2014,40(2):252-259.
23.Ali M T,Fule R,Sav A,et al.Porous starch:a novel carrier for solubility enhancement of carbamazepine[J].AAPSPharm Sci Tech,2013,14(3):919-926.
24.Gao F,Li D,Bi C H,et al.The adsorption and release characteristics of CPFX in porous starch produced through different drying methods[J].Drying Technology,2013,31(13-14):1592-1599.
25.唐宜轩,韩丽,张定堃,等.多孔淀粉的制备及其在医药应用中的研究进展[J].中成药,2015,37(6):1321-1324.Tang Y X,Han L,Zhang D K,et al.Preparation of porous starch and its application in medicine[J].Chinese Traditional Patent Medicine,2015,37(6):1321-1324.
26.Ali M T,Fule R,SAV A,et al.Porous starch:a novel carrier for solubility enhancement of carbamazepine[J].AAPSPharm Sci Tech,2013,14(3):919-926.
27.Zhang Z W,Huang J,Jiang S J,et al.Porous starch based self-assembled nano-delivery system improves the oral absorption of lipophilic drug[J].International Journal of Pharmaceutics,2013,444(1-2):162-168.
28.Deng X R,Liu Z X,Liu F,et al.Holotransferrin enhances selective anticancer activity of artemisinin against human hepatocellular carcinoma cells[J].Journal of Huazhong U-niversity of Science and Technology[Medical Sciences],2013,33(6):862-865.