Noscapine shows antimalarial activity against Plasmodium falciparum 3D7,its clinical isolate Pf140/SS,and Plasmodium berghei ANKA

Objective:To evaluate the antimalarial activity of noscapine against Plasmodium falciparum 3D7 strain(Pf3D7),its clinical isolate(Pf140/SS),and Plasmodium berghei ANKA(PbA).Methods:Using ring-stage survival assay,phenotypic assessments,and SYBR-green-based fluorescence assay,the antimalarial activities of noscapine were assessed compared with dihydroartemisinin(DHA)in in vivo and in vitro studies.In addition,hemolysis and cytotoxicity tests were carried out to evaluate its safety.RT-PCR assay was also conducted to determine the effect of noscapine on papain-like cysteine protease Plasmodium falciparum falcipain-2(PfFP-2).Results:The antimalarial efficacy of noscapine against Pf3D7 and Pf140/SS was comparable to DHA,with IC50 values of(7.68±0.88)and(5.57±0.74)nM/mL,respectively,and>95%inhibition of PbA infected rats.Noscapine also showed a safe profile,as evidenced by low hemolysis and cytotoxicity even at high concentrations.Moreover,PfFP-2 expression was significantly inhibited in both noscapine-treated Pf3D7 and Pf140/SS(P<0.01).Conclusions:Noscapine has antimalarial properties comparable to standard antimalarial DHA with better safety profiles,which may be further explored as a therapeutic candidate for the treatment of malaria.

人结肠癌那可丁耐药细胞株HT-29/Nos、LoVo/Nos、SW480/Nos的构建及其生物特性探究

目的构建那可丁(Nos)耐药的人结肠癌细胞株(HT-29/Nos、LoVo/Nos、SW480/Nos),探究细胞株的生物学特性。方法采用反复大剂量结合药物浓度梯度法建立人结肠癌耐药细胞株HT-29/Nos、LoVo/Nos、SW480/Nos。CCK-8法检测Nos对人结肠癌细胞株HT-29、LoVo、SW480和耐药细胞株HT-29/Nos、LoVo/Nos、SW480/Nos细胞的半数抑制率(IC_(50))。细胞生长曲线的测定。流式细胞术测定各组细胞株的细胞周期变化。Real time PCR和Western blot分别检测耐药相关基因和蛋白的表达。结果成功构建人结肠癌耐药细胞株HT-29/Nos、LoVo/Nos、SW480/Nos,耐药指数分别为6.37、7.15、6.81。HT-29/Nos细胞倍增时间较HT-29显著增长[(51.42±2.83)h vs(35.05±3.61)h,P<0.05];LoVo/Nos细胞倍增时间较LoVo显著增长[(61.93±4.22)h vs(38.38±1.88)h,P<0.05];SW480/Nos细胞倍增时间较SW480增长[(48.84±1.40)h vs(31.30±1.75)h,P<0.05]。耐药细胞株HT-29/Nos、LoVo/Nos、SW480/Nos的G_1期细胞数目显著增加(P<0.05),S期细胞数目显著减少(P<0.05)。耐药细胞株HT-29/Nos、LoVo/Nos、SW480/Nos的P-gp和MDR-1 mRNA和蛋白表达均高于HT-29、LoVo、SW480细胞株。结论成功构建了Nos耐药人结肠癌细胞株HT-29/Nos、LoVo/Nos、SW480/Nos,为下一步耐药性分子机制的研究奠定基础。