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??OBJECTIVE To investigate the synergetic effect of schisandrin B and liposomes on overcoming multidrug resistance(MDR). METHODS Co-delivery of doxorubicin and schisandrin B by liposome(DS-L) were prepared, and doxorubicin solution(F-DOX), schisandrin B and doxorubicin mixture(Sch B+DOX), doxorubicin liposomes(D-L), doxorubicin liposomes and schisandrin B mixture(D-L+Sch B), verapamil and doxorubicin mixture(Ver+DOX) were also prepared as the control. The MTT test were measured, and the amount of doxorubicin in the K562/DOX cells at different time were determined, and time course of uptake and efflux were drawn. RESULTS The MTT test shows that the resistance factor(RF) of group DS-L were 1.68, 14.52 and 1.42 times of group Sch B+DOX, group D-L and group D-L+Sch B respectively. The uptake test shows that amount of doxorubicin of K562/DOX cells in group DS-L was 1.30 and 1.21 times of that in group D-L and group Sch B+DOX respectively. And the efflux test shows DS-L could delay doxorubicin efflux from K562/DOX cells. CONCLUSION The co-delivery of chemotherapeutics and P-gp inhibitors schisandrin B by liposome is a promising approach to overcome MDR. And there is a synergistic effect between liposome and schisandrin B to overcome MDR.     

Cariporide降低K562/DOX细胞株表达P-糖蛋白而逆转耐药的影响

 目的 探讨cariporide对耐药细胞株K562/DOX中P-糖蛋白（P-glycoprotein,P-gp）的影响,为抗白血病多药耐药（multidrug resistance, MDR）提供新方法。方法 应用cariporide对细胞进行酸化,应用激光共聚焦显微镜测定野生型细胞系K562及耐药细胞株K562/DOX细胞内pH值及细胞酸化对K562和K562/DOX细胞内阿霉素累积的影响。采用MTT法观察细胞酸化对细胞活力的影响。应用流式细胞术检测细胞酸化对K562/DOX细胞中P-gp功能的影响。采用实时定量RT-PCR技术检测MDR1基因在mRNA表达水平的变化。结果 Cariporide处理3 h对K562及K562/DOX细胞的活力影响较小。在K562/DOX细胞中,P-gp的外排药物能力随细胞内pH值的降低而减弱,cariporide明显增加了细胞对罗丹明123（rhodaminel 123,Rh123）和阿霉素的累积。细胞酸化还在mRNA水平抑制了K562/DOX细胞中P-gp的表达。结论 Cariporide能够抑制K562/DOX耐药细胞株中MDR1基因表达和P-gp的功能。     

小檗碱增强K562/DOX细胞对多柔比星敏感性的研究

 目的 探讨小檗碱增强耐药K562/DOX细胞对化疗药多柔比星的敏感性的作用。方法 四甲基偶氮唑蓝法检测小檗碱的细胞毒性及其对多柔比星抗肿瘤活性的增强作用;高内涵活细胞成像系统检测无毒剂量小檗碱作用后,多柔比星在K562/DOX细胞内的蓄积量;PI/Hoechst33342双染法检测小檗碱对多柔比星诱导的K562/DOX细胞凋亡的影响;罗丹明123蓄积实验检测小檗碱对P-糖蛋白外排功能的影响。结果 1 μmol·L^-1为小檗碱的无毒剂量,在此无毒剂量下,小檗碱使多柔比星对K562/DOX细胞的IC₅₀降低了1.5倍;1 μmol·L^-1小檗碱可使多柔比星在K562/DOX细胞内的蓄积量增加,增强多柔比星诱导的K562/DOX细胞凋亡, 增加K562/DOX细胞内罗丹明123的蓄积量,从而抑制P-糖蛋白的外排功能。结论 小檗碱可通过抑制K562/DOX细胞膜上P-糖蛋白的外排功能,增加K562/DOX细胞内多柔比星浓度,促进多柔比星对耐药细胞的诱导凋亡作用,逆转K562/DOX细胞的多药耐药性。     

欧白芷素对K562/A02细胞阿霉素耐药的逆转作用(英文)

目的:探讨欧白芷素对耐药细胞株K562/A02中P-糖蛋白(P-glycoprotein,P-gp)的影响,为抗白血病多药耐药(multi-drug resistance,MDR)提供新方法。方法:采用MTT法观察阿霉素对细胞活力的影响。应用流式细胞术检测欧白芷素对K562和K562/A02细胞内阿霉素累积和细胞中P-gp功能的影响。采用实时定量RT-PCR技术检测MDR1基因在mRNA表达水平的变化。结果:欧白芷素对耐药细胞株K562/A02有显著的逆转耐药活性,最大逆转倍数为7.36。在K562/A02细胞中,欧白芷素明显增加阿霉素的累积,增加了罗丹明123(rhodaminel123,Rh123)蓄积,抑制了Rh123的外排,同时欧白芷素还在mRNA水平抑制了K562/A02细胞中P-gp的表达。结论:欧白芷素能够抑制K562/A02耐药细胞株中MDR1基因表达和P-gp的功能。     

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??Multidrug resistance (MDR) is one of the major obstacles for successful chemotherapy in cancer. Inorganic material-based nanoparticles provide a novel choice to effectively circumvent the intrinsic drawbacks of traditional organic materials in overcoming the multidrug resistance (MDR) of cancer cells due to their unique structural and compositional characteristics,for example,high stability,large surface area,tunable compositions,abundant physicochemical multifunctionalities,and specific biological behaviors. In this work,the recent advances of inorganic materials-based nanoparticles to overcome MDR of cancer cells were reviewed. And the advantage and mechanism of inorganic materials-based nanoparticles to overcome MDR were summarized. The recent development of inorganic materials-based nanoparticles (mesoporous SiO₂,Au,TiO₂,magnetic Fe₃O₄,Ag,combinations of inorganic materials-based nanoparticles with traditional overcoming MDR strategy etc.),to overcome the MDR were also discussed. And the future developments of these inorganic materials-based nanoparticles are suggested. These elaborately designed inorganic materials-based nanoparticles offer an unprecedented opportunity and show the encouraging bright future for overcoming the MDR of tumors.     

通关藤中4种C21甾体化合物逆转卵巢癌细胞紫杉醇耐药的作用评价

目的 评价通关藤中4种C₂₁甾体化合物(通关藤苷I、通关藤苷G、通关藤苷H和17β-通关藤苷元B)对人卵巢癌紫杉醇耐药细胞A2780/Taxol(A2780/T)耐药的逆转作用及相关机制。方法 将人卵巢癌A2780/T细胞分为对照组、C₂₁甾体单用组、紫杉醇单用组、C₂₁甾体联合紫杉醇组(1:1),MTT法检测细胞增殖能力,中效原理分析两药联用效应(Fa)与合用指数(CI)的关系;划痕实验观察细胞迁移能力;流式细胞术及Hoechst 33258染色检测细胞周期和凋亡情况;RT-PCR、Western blot法分别检测ABCB1、SLC4A2、SLCO1A2 mRNA及P-gp表达水平;药物外排实验检测A2780/T细胞内紫杉醇及罗丹明123的蓄积量。结果 4种C₂₁甾体单用或与紫杉醇联用均能抑制A2780/T细胞增殖,且呈剂量依赖效应。通关藤苷G、通关藤苷H与紫杉醇联用48 h具有协同效应,能够显著抑制A2780/T细胞迁移、阻滞细胞于G2/M期、促进细胞凋亡,显著抑制ABCB1、SLC4A2、SLCO1A2 mRNA水平,下调P-gp表达,显著促进了紫杉醇及罗丹明123在A2780/T细胞内的蓄积。结论 通关藤苷G、通关藤苷H与紫杉醇联用均产生协同效应,可逆转人卵巢癌A2780/T细胞对紫杉醇的耐药性,其机制可能与降低基因ABCB1、SLC4A2、SLCO1A2及P-gp的表达水平,促进紫杉醇在A2780/T细胞内蓄积有关。     

六神丸逆转K562/DOX细胞阿霉素耐药的研究

目的:探讨六神丸对阿霉素耐药细胞株K562/DOX的耐药逆转作用。方法:MTT法检测单独应用阿霉素或阿霉素联合六神丸含药血清对K562/DOX细胞的生存率的影响;RT-PCR检测MDR1 mRNA表达;Western blot检测MDR1蛋白的表达。结果:阿霉素与六神丸含药血清联合作用:①细胞抑制率最高,最高值出现在72h(49.4%),且与对照组和单独应用阿霉素组相比有显著性差异;②48h细胞MDR1 mRNA表达明显降低,与单独应用阿霉素组相比有显著性差异;③48h细胞MDR1蛋白表达下降,且与对照组和单独应用阿霉素组相比有显著性差异。结论:六神丸可能通过下调MDR1表达水平进而逆转K562/DOX细胞对阿霉素的耐药性,增加肿瘤耐药细胞对化疗药物的敏感性。     

槲皮素和山柰酚逆转白血病细胞系K562/A02多药耐药性的机制及相关基因表达谱的研究

目的研究槲皮素(quercetin,Que)及山柰酚(kaempferol,Kae)单用及联合应用时对K562/A02细胞系多药耐药的影响及机制。方法体外培养K562和K562/A02细胞经Que及Kae处理,采用噻唑蓝(MTT)法计算药物单独及联合作用后细胞的生长抑制率及对多柔比星(adriamycin,ADM)的增敏倍数;流式细胞术检测药物作用后细胞内ADM浓度的变化;Annexin V/PI法观察细胞凋亡情况;Real-time PCR基因芯片检测药物转运蛋白及凋亡相关基因表达的变化。结果药物作用48 h后,Que及Kae在5～160μmol.L-1时对K562和K562/A02细胞均有剂量依赖性的生长抑制作用,K562/A02对ADM的敏感性显著增强,二者联用效果有协同性;在ADM为5μmol.L-1时,药物与细胞共培养2 h即可检出Que能增加细胞内ADM的浓度,而Kae则对ADM浓度无明显影响,两药联合作用的效果不及Que单独作用。Que和Kae均可剂量依赖性地诱导K562和K562/A02细胞的凋亡。二者可影响ABC、SLC家族等药物转运蛋白相关基因的表达,并可调节Bcl-2、TNF等凋亡相关基...     

复方中药紫龙金克服肿瘤细胞多药耐药性的机制

目的探讨中药紫龙金(Zilongjin,ZLJ)对多药耐药肿瘤细胞的作用机制。方法采用MTT法检测ZLJ对细胞增殖的影响;流式细胞术检测细胞周期以及罗丹明123的荧光强度变化;Western blot方法检测相关蛋白的表达变化。结果 ZLJ分别处理人乳腺癌MCF-7和MCF-7/DOX耐药细胞,以及人口腔上皮癌KB和KBV200耐药细胞。MTT法测定表明:ZLJ作用耐药和敏感细胞的IC50值相近,耐药细胞对ZLJ没有交叉耐药性;无论对敏感和耐药细胞,流式细胞术分析发现ZLJ阻断细胞于S期;ZLJ单独处理MCF-7/DOX和KBV200耐药细胞,可以微弱地降低其耐药性,分别与多柔比星(doxorubicin,DOX)和长春新碱(vincris-tine,VCR)合用,可以明显地增加DOX和VCR的活性;ZLJ处理耐药细胞MCF-7/DOX后,检测到细胞内耐药蛋白P-糖蛋白(P-glyco protein,P-gp)呈时间依赖性降低。Western blot检测表明,ZLJ的抑制作用是通过使凋亡标志蛋白PARP出现切割,启动凋亡通路实现的。结论中药ZLJ抑制耐药细胞增殖,没有交叉耐药性;其抑制作用与诱导细胞凋亡以及降低P-gp表达有关。