Multidrug resistance(MDR)is a serious obstacle encountered in cancer treatment.This study was performed to explore the reversal MDR activity of ivermectin(IVM)from avermectin family and moxidectin(MOX)belonging to mil...Multidrug resistance(MDR)is a serious obstacle encountered in cancer treatment.This study was performed to explore the reversal MDR activity of ivermectin(IVM)from avermectin family and moxidectin(MOX)belonging to milbemycin family.The two compounds(5μmol•L-1)showed strong potency to increase adriamycin cytotoxicity toward adriamycin-resistant rat glioma cells C6/adr with fold reversal(FR)of 31.02 and 13.40,respectively.In addition,the mechanisms of them on p-glycoprotein(P-gp)-mediated MDR demonstrated that the two compounds significantly increased the intracellular accumulations of adriamycin and Rh123 via inhibiting P-gp efflux.Based on the analysis of P-gp,MDR1 and MRP1 gene expressions by using immunofluorescence flow cytometry and RT-PCR,the results revealed that the two compounds could down regulate the expression of P-gp,and that MDR1 and MRP1 gene expressions were down regulated.These findings suggested that ivermectin and moxidectin probably represented potent agents for reversing MDR in cancer therapy,and especially ivermectin was a better modulator.展开更多
Loss of efficacy due to resistance development against anthelmintics in livestock parasites is a growing concern worldwide. The aim of the present study was to determine the efficacy of moxidectin, a frequently-used m...Loss of efficacy due to resistance development against anthelmintics in livestock parasites is a growing concern worldwide. The aim of the present study was to determine the efficacy of moxidectin, a frequently-used macrocyclic lactone, against gastrointestinal nematodes of sheep in Austria. Individual faecal samples were collected from 243 adult sheep from 16 flocks in Styria and Salzburg before deworming and egg excretion （EPG （eggs per gram） of faeces） was determined using a modified McMaster technique. The animals were randomly assigned to a treatment group which received 0.2 mg/kg of body weight of moxidectin （Cydectin , Zoetis Schweiz GmbH, Zurich, Switzerland）, and an untreated control group. Fourteen days after deworming a FECRT （faecal egg count reduction test） for detection of anthelmintic resistance was performed. Before deworming, the infection rate for gastrointestinal strongylids was 94.7%, with EPG values of 0-5,800. The FECRT showed reduction rates between 93.08% and 99.78% and was sufficient in 15/16 flocks. The lower confidence interval was 70.0-100%. In 3/16 flocks this value was below the minimum for sufficient efficacy （70.0%, 79.0%, 85.0%）, and in two flocks the value （90,0%） was near the limit. These results indicated a （suspected） reduced efficacy of moxidectin in 5/16 examined flocks.展开更多
基金Supported by the National Natural Science Foundation of China(81201723)。
文摘Multidrug resistance(MDR)is a serious obstacle encountered in cancer treatment.This study was performed to explore the reversal MDR activity of ivermectin(IVM)from avermectin family and moxidectin(MOX)belonging to milbemycin family.The two compounds(5μmol•L-1)showed strong potency to increase adriamycin cytotoxicity toward adriamycin-resistant rat glioma cells C6/adr with fold reversal(FR)of 31.02 and 13.40,respectively.In addition,the mechanisms of them on p-glycoprotein(P-gp)-mediated MDR demonstrated that the two compounds significantly increased the intracellular accumulations of adriamycin and Rh123 via inhibiting P-gp efflux.Based on the analysis of P-gp,MDR1 and MRP1 gene expressions by using immunofluorescence flow cytometry and RT-PCR,the results revealed that the two compounds could down regulate the expression of P-gp,and that MDR1 and MRP1 gene expressions were down regulated.These findings suggested that ivermectin and moxidectin probably represented potent agents for reversing MDR in cancer therapy,and especially ivermectin was a better modulator.
文摘Loss of efficacy due to resistance development against anthelmintics in livestock parasites is a growing concern worldwide. The aim of the present study was to determine the efficacy of moxidectin, a frequently-used macrocyclic lactone, against gastrointestinal nematodes of sheep in Austria. Individual faecal samples were collected from 243 adult sheep from 16 flocks in Styria and Salzburg before deworming and egg excretion （EPG （eggs per gram） of faeces） was determined using a modified McMaster technique. The animals were randomly assigned to a treatment group which received 0.2 mg/kg of body weight of moxidectin （Cydectin , Zoetis Schweiz GmbH, Zurich, Switzerland）, and an untreated control group. Fourteen days after deworming a FECRT （faecal egg count reduction test） for detection of anthelmintic resistance was performed. Before deworming, the infection rate for gastrointestinal strongylids was 94.7%, with EPG values of 0-5,800. The FECRT showed reduction rates between 93.08% and 99.78% and was sufficient in 15/16 flocks. The lower confidence interval was 70.0-100%. In 3/16 flocks this value was below the minimum for sufficient efficacy （70.0%, 79.0%, 85.0%）, and in two flocks the value （90,0%） was near the limit. These results indicated a （suspected） reduced efficacy of moxidectin in 5/16 examined flocks.
