Objective： To explore the relationship between survivin and drug resistance, and the changes of the survivin expression in HL-60 cells treated with three kinds of chemotherapeutic drugs. Methods： HL- 60 cells were t...Objective： To explore the relationship between survivin and drug resistance, and the changes of the survivin expression in HL-60 cells treated with three kinds of chemotherapeutic drugs. Methods： HL- 60 cells were treated with appropriate concentration of daunomycin （DNR）, mitoxantrone （MIT） or arsenic trioxide （As2O3）. The expression of survivin mRNA and protein on the first or third day was detected by RT-PCR and Western blot respectively. Results： The expression of survivin mRNA was decreased on the first day by 10% in DNR-treated group, 40% in MIT-treated group （P〈0.01） and 25% in As2O3-treated group （P〈0.01） respectively. On the third day, the expression of survivin mRNA in DNR- and MIT-treated group was up-regulated to 120% （P〈0.05） and 165% （P〈0.01） respectively as compared with that on the first day, but down-regulated to 68% in As2O3-treated group （P〈0.01）. As compared with control group, the expression of survivin protein in DNR- or MIT-treated group was increased by 14% or 11% on the third day respectively, but it was decreased by 18% in As2O3-treated group. Conclusion： In DNR- and MIT-treated group, the expression of surivin was decreased at first and then increased obviously, which may be one of the causes for resistance to chemotherapy against leukemia. Different from other two drugs, As2O3 may play an important role in restoring chemotherapy sensitivity.展开更多
The distribution of ￣(3)H-mitoxantrone polybutyl cyanoacrylate nanospheres(￣(3)H-DHAQ-PBCA-NS)in the viscera,muscle and tumors of human hepatocellular carcinoma (HCC)model in nude mice was studied with liquid scinti...The distribution of ￣(3)H-mitoxantrone polybutyl cyanoacrylate nanospheres(￣(3)H-DHAQ-PBCA-NS)in the viscera,muscle and tumors of human hepatocellular carcinoma (HCC)model in nude mice was studied with liquid scintillation counting techniique. The results showed that the ￣(3)H-DHAQ-PBCA-NS had remarkable liver targeting effect. The content of ￣(3)H-DHAQ-PBCA-NSin liver and heterotopic liver tumor was found to be 71.31±10. 49% of total amount of drug in animal body. It was also found that the content of ￣(3)H-DHAQ-PBCA-NS in liver was higher than that in liver tissue, and the content of ￣(3)H-DHAQ-PBCA-NS in annpit tumor was higher than that in armpit muscle tissue,but had no significant difference;It provides an ideal preparation for the DHAQ admini-stration.展开更多
Herein,the orthogonal test was used to optimize the preparation conditions and technique of mitoxantrone ethylcellulose microsphere fDHAQ-EC-MS)for liver arterial embolization.The dynamic dialysis method was used to s...Herein,the orthogonal test was used to optimize the preparation conditions and technique of mitoxantrone ethylcellulose microsphere fDHAQ-EC-MS)for liver arterial embolization.The dynamic dialysis method was used to study the drug release characteristics ofthe DRAQ-EC-MS.The suspension of DHAQ-EC-MS for clinical liver arterial embolization was prepared.The results show that the DHAQ-EC-MS is regular in morphology with a mean diameter of 110.24 ± 38.19μm and 86.5% of them within the range of 40-150μm,The drug loading is 12.5% and the embedding ratio is 55.6%. The release characteristics were in accordance with the single exponential model.The drug release equation is log(Y∞-Y)=-0.116t-1.198 × 10￣(-3)(r=0.9992,t(50)=2.6h).The suspension is ofstable physical and chemical properties and is suitable for clinical use.展开更多
Folic acid conjugated chitosan was prepared by cross-linking reaction with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride(EDC), and then used as a template to prepare folic acid-chitosan(FA-CS) conjugate...Folic acid conjugated chitosan was prepared by cross-linking reaction with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride(EDC), and then used as a template to prepare folic acid-chitosan(FA-CS) conjugated nanoparticles and load mitoxantrone nanoparticles(FA-CSNP/MTX). Drug dissolution testing, CCK-8 method, and confocal microscopy were used to detect their controlled-release capability in different situations and the specific uptake by HONE1 cells. The experimental results show that the nanoparticles have uniform size distribution of 48-58 nm. The highest encapsulation rate of the particles on mitoxantrone hydrochloride(MTX) is(77.5±1.9)%, and the drug loading efficiency is(18.4±0.4)%. The sustained release effect, cell growth inhibition activity and targeting effect of the FA-CS/MTX nanoparticles are good in artificial gastric fluid and intestinal fluid. It is demonstrated that the FA-CSNP system is a potentially useful system for the targeted delivery of anticancer drug MTX.展开更多
基金This project was supported by a grant from the National Natural Sciences Foundation of China (No. 30370595).
文摘Objective： To explore the relationship between survivin and drug resistance, and the changes of the survivin expression in HL-60 cells treated with three kinds of chemotherapeutic drugs. Methods： HL- 60 cells were treated with appropriate concentration of daunomycin （DNR）, mitoxantrone （MIT） or arsenic trioxide （As2O3）. The expression of survivin mRNA and protein on the first or third day was detected by RT-PCR and Western blot respectively. Results： The expression of survivin mRNA was decreased on the first day by 10% in DNR-treated group, 40% in MIT-treated group （P〈0.01） and 25% in As2O3-treated group （P〈0.01） respectively. On the third day, the expression of survivin mRNA in DNR- and MIT-treated group was up-regulated to 120% （P〈0.05） and 165% （P〈0.01） respectively as compared with that on the first day, but down-regulated to 68% in As2O3-treated group （P〈0.01）. As compared with control group, the expression of survivin protein in DNR- or MIT-treated group was increased by 14% or 11% on the third day respectively, but it was decreased by 18% in As2O3-treated group. Conclusion： In DNR- and MIT-treated group, the expression of surivin was decreased at first and then increased obviously, which may be one of the causes for resistance to chemotherapy against leukemia. Different from other two drugs, As2O3 may play an important role in restoring chemotherapy sensitivity.
文摘The distribution of ￣(3)H-mitoxantrone polybutyl cyanoacrylate nanospheres(￣(3)H-DHAQ-PBCA-NS)in the viscera,muscle and tumors of human hepatocellular carcinoma (HCC)model in nude mice was studied with liquid scintillation counting techniique. The results showed that the ￣(3)H-DHAQ-PBCA-NS had remarkable liver targeting effect. The content of ￣(3)H-DHAQ-PBCA-NSin liver and heterotopic liver tumor was found to be 71.31±10. 49% of total amount of drug in animal body. It was also found that the content of ￣(3)H-DHAQ-PBCA-NS in liver was higher than that in liver tissue, and the content of ￣(3)H-DHAQ-PBCA-NS in annpit tumor was higher than that in armpit muscle tissue,but had no significant difference;It provides an ideal preparation for the DHAQ admini-stration.
文摘Herein,the orthogonal test was used to optimize the preparation conditions and technique of mitoxantrone ethylcellulose microsphere fDHAQ-EC-MS)for liver arterial embolization.The dynamic dialysis method was used to study the drug release characteristics ofthe DRAQ-EC-MS.The suspension of DHAQ-EC-MS for clinical liver arterial embolization was prepared.The results show that the DHAQ-EC-MS is regular in morphology with a mean diameter of 110.24 ± 38.19μm and 86.5% of them within the range of 40-150μm,The drug loading is 12.5% and the embedding ratio is 55.6%. The release characteristics were in accordance with the single exponential model.The drug release equation is log(Y∞-Y)=-0.116t-1.198 × 10￣(-3)(r=0.9992,t(50)=2.6h).The suspension is ofstable physical and chemical properties and is suitable for clinical use.
基金Projects(31201074,81371013) supported by the National Natural Science Foundation of ChinaProject(2011105102016) supported by the Key Program of Medical Health of Dongguan City,Guangdong Province,ChinaProject(2011108102026) supported by Dongguan Universities Program,China
文摘Folic acid conjugated chitosan was prepared by cross-linking reaction with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride(EDC), and then used as a template to prepare folic acid-chitosan(FA-CS) conjugated nanoparticles and load mitoxantrone nanoparticles(FA-CSNP/MTX). Drug dissolution testing, CCK-8 method, and confocal microscopy were used to detect their controlled-release capability in different situations and the specific uptake by HONE1 cells. The experimental results show that the nanoparticles have uniform size distribution of 48-58 nm. The highest encapsulation rate of the particles on mitoxantrone hydrochloride(MTX) is(77.5±1.9)%, and the drug loading efficiency is(18.4±0.4)%. The sustained release effect, cell growth inhibition activity and targeting effect of the FA-CS/MTX nanoparticles are good in artificial gastric fluid and intestinal fluid. It is demonstrated that the FA-CSNP system is a potentially useful system for the targeted delivery of anticancer drug MTX.
