目的探讨五味子甲素(schizandrin A or deoxyschizan-drin,schA)对白血病细胞K562/ADR、HL60/ADR、乳腺癌细胞MCF-7/ADR多药耐药的逆转作用,并初步探讨其逆转机制。方法 MTT法检测schA对耐药细胞的逆转作用;流式细胞仪检测schA对细胞内...目的探讨五味子甲素(schizandrin A or deoxyschizan-drin,schA)对白血病细胞K562/ADR、HL60/ADR、乳腺癌细胞MCF-7/ADR多药耐药的逆转作用,并初步探讨其逆转机制。方法 MTT法检测schA对耐药细胞的逆转作用;流式细胞仪检测schA对细胞内柔红霉素、罗丹明-123含量和细胞表面P-gp表达水平的变化;用Real-time PCR方法检测schA对细胞内mdr1 mRNA和mrp1 mRNA表达;生化检测法检测schA对细胞内GSH含量的变化。结果耐药逆转实验显示:不同浓度的schA对作用机制不同的化疗药物耐药产生不同的逆转效果;蓄积实验表明schA可增加柔红霉素、罗丹明123在耐药细胞内的蓄积,并且有良好的剂量依赖关系;schA处理K562/ADR、HL60/ADR细胞24 h后,能降低P-gp蛋白和mdr1、mrp1基因的表达;schA处理K562/ADR、HL60/ADR细胞4 h后,可降低细胞内谷胱甘肽含量。结论 schA对耐药机制不同的细胞株K562/ADR、HL60/ADR均有耐药逆转作用,推测可能是与抑制细胞表面的P-gp蛋白功能和表达,降低mdr1、mrp1耐药基因的表达和降低细胞内谷胱甘肽含量有关,schA通过影响上述机制,进而增加细胞内的药物浓度,达到有效杀灭肿瘤细胞的作用。展开更多
Background and Objective:Chemotherapy is the main treatment for colon cancer,while multidrugresistance is the main reason for chemotherapy failure and tumor relapse.This study was to establish two oxaliplatinresistant...Background and Objective:Chemotherapy is the main treatment for colon cancer,while multidrugresistance is the main reason for chemotherapy failure and tumor relapse.This study was to establish two oxaliplatinresistant colon cancer cell lines and evaluate their biological characteristics.Met hods:Oxaliplatin-resistant colon cancer cell lines SW620/L-OHP and lovo/L-OHP were established in vitro by continuous exposure to oxaliplatin(L-OHP) of low and gradually increased concentration.Growth curve,cross-resistance and resistance index of the oxaliplatin-resistant cell lines to various anti-cancer agents were determined by CCK8 assay.The expressions of P-glycoprotein(P-gp),multidrugresistance protein 1(MRP1) and MRP2 were detected by Western blot.Cell cycle distribution as well as the expression of CD133 and CD44 were measured by flow cytometry.Result s:It took 10 months to establish the SW620/L-OHP and LoVo/L-OHP cell lines with stable resistance to oxaliplatin.Cross-resistance to 5-fluorouracil,etoposide,cisplatin,vincristine and epirubicin but not to paclitaxel was observed.Longer doubling time,higher proportion of cells in G0/G1 phase and lower proportion in G2/M phase were observed in the two oxaliplatin-resistant cell lines compared with their parental cell lines.The expression of MRP2 in the oxaliplatin-resistant cells was up-regulated,while those of P-gp and MRP1 had no significant change.CD133 was overexpressed while CD44 level remained unchanged in SW620/L-OHP and LoVo/L-OHP cells.Conclusions:SW620/L-OHP and LoVo/L-OHP cell lines show a typical and stably resistant phenotype and may be used as research models.展开更多
Multidrug resistance(MDR) is one of the major obstacles in cancer chemotherapy. Our previous study has shown that icariin could reverse MDR in MG-63 doxorubicin-resistant(MG-63/DOX) cells. It is reported that icariin ...Multidrug resistance(MDR) is one of the major obstacles in cancer chemotherapy. Our previous study has shown that icariin could reverse MDR in MG-63 doxorubicin-resistant(MG-63/DOX) cells. It is reported that icariin is usually metabolized to icariside II and icaritin. Herein, we investigated the effects of icariin, icariside Ⅱ, and icaritin(ICT) on reversing MDR in MG-63/DOX cells. Among these compounds, ICT exhibited strongest effect and showed no obvious cytotoxicity effect on both MG-63 and MG-63/DOX cells ranging from 1 to 10 μmol·L^(-1). Furthermore, ICT increased accumulation of rhodamine 123 and 6-carboxyfluorescein diacetate and enhanced DOX-induced apoptosis in MG-63/DOX cells in a dose-dependent manner. Further studies demonstrated that ICT decreased the m RNA and protein levels of multidrug resistance protein 1(MDR1) and multidrug resistance-associated protein 1(MRP1). We also verified that blockade of STAT3 phosphorylation was involved in the reversal effect of multidrug resistance in MG-63/DOX cells. Taken together, these results indicated that ICT may be a potential candidate in chemotherapy for osteosarcoma.展开更多
目的探讨胆盐载体MRP1、MRP2在妊娠期肝内胆汁淤积症(ICP)胎盘的表达,分析胎盘胆盐载体与ICP发病的关系。方法收集8例正常早孕妇女绒毛组织、7例正常中孕妇女胎盘组织、20例正常晚孕妇女(对照组)胎盘组织,以及20例ICP患者胎盘组织,检测...目的探讨胆盐载体MRP1、MRP2在妊娠期肝内胆汁淤积症(ICP)胎盘的表达,分析胎盘胆盐载体与ICP发病的关系。方法收集8例正常早孕妇女绒毛组织、7例正常中孕妇女胎盘组织、20例正常晚孕妇女(对照组)胎盘组织,以及20例ICP患者胎盘组织,检测收集组织中胆盐载体MRP1和MRP2 mRNA的表达。结果ICP和正常妊娠各期胎盘组织中均有MRP2 mRNA的表达,而MRP1 mRNA在大部分标本上有表达;ICP组MRP1 mRNA和MRP2 mRNA表达量与对照组相比(99.94±73.17 vs 99.20±68.65;95.78±56.50 vs 142.20±91.27)差异无统计学意义(P>0.05);ICP组未用地塞米松治疗胎盘MRP2 mRNA表达量低于对照组(91.82±48.08 vs 142.20±91.27,P<0.05)。结论在未用地塞米松治疗的ICP患者胎盘组织中,MRP2 mRNA的表达量降低,这可能是引起ICP患者胎盘胆汁酸转运障碍,从而引起胎儿体内胆汁淤积的机制之一。展开更多
基金National Natural Science Foundation of China (No. 30901719,No.30971519)
文摘Background and Objective:Chemotherapy is the main treatment for colon cancer,while multidrugresistance is the main reason for chemotherapy failure and tumor relapse.This study was to establish two oxaliplatinresistant colon cancer cell lines and evaluate their biological characteristics.Met hods:Oxaliplatin-resistant colon cancer cell lines SW620/L-OHP and lovo/L-OHP were established in vitro by continuous exposure to oxaliplatin(L-OHP) of low and gradually increased concentration.Growth curve,cross-resistance and resistance index of the oxaliplatin-resistant cell lines to various anti-cancer agents were determined by CCK8 assay.The expressions of P-glycoprotein(P-gp),multidrugresistance protein 1(MRP1) and MRP2 were detected by Western blot.Cell cycle distribution as well as the expression of CD133 and CD44 were measured by flow cytometry.Result s:It took 10 months to establish the SW620/L-OHP and LoVo/L-OHP cell lines with stable resistance to oxaliplatin.Cross-resistance to 5-fluorouracil,etoposide,cisplatin,vincristine and epirubicin but not to paclitaxel was observed.Longer doubling time,higher proportion of cells in G0/G1 phase and lower proportion in G2/M phase were observed in the two oxaliplatin-resistant cell lines compared with their parental cell lines.The expression of MRP2 in the oxaliplatin-resistant cells was up-regulated,while those of P-gp and MRP1 had no significant change.CD133 was overexpressed while CD44 level remained unchanged in SW620/L-OHP and LoVo/L-OHP cells.Conclusions:SW620/L-OHP and LoVo/L-OHP cell lines show a typical and stably resistant phenotype and may be used as research models.
基金supported by the National Natural Science Foundation of China(Nos.81673554 and 81503211)Natural Science Foundation of Jiangsu Province(No.BK20160763)+1 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)the Program for Changjiang Scholars and Innovative Research Team in University(No.IRT_15R63)
文摘Multidrug resistance(MDR) is one of the major obstacles in cancer chemotherapy. Our previous study has shown that icariin could reverse MDR in MG-63 doxorubicin-resistant(MG-63/DOX) cells. It is reported that icariin is usually metabolized to icariside II and icaritin. Herein, we investigated the effects of icariin, icariside Ⅱ, and icaritin(ICT) on reversing MDR in MG-63/DOX cells. Among these compounds, ICT exhibited strongest effect and showed no obvious cytotoxicity effect on both MG-63 and MG-63/DOX cells ranging from 1 to 10 μmol·L^(-1). Furthermore, ICT increased accumulation of rhodamine 123 and 6-carboxyfluorescein diacetate and enhanced DOX-induced apoptosis in MG-63/DOX cells in a dose-dependent manner. Further studies demonstrated that ICT decreased the m RNA and protein levels of multidrug resistance protein 1(MDR1) and multidrug resistance-associated protein 1(MRP1). We also verified that blockade of STAT3 phosphorylation was involved in the reversal effect of multidrug resistance in MG-63/DOX cells. Taken together, these results indicated that ICT may be a potential candidate in chemotherapy for osteosarcoma.
文摘目的探讨胆盐载体MRP1、MRP2在妊娠期肝内胆汁淤积症(ICP)胎盘的表达,分析胎盘胆盐载体与ICP发病的关系。方法收集8例正常早孕妇女绒毛组织、7例正常中孕妇女胎盘组织、20例正常晚孕妇女(对照组)胎盘组织,以及20例ICP患者胎盘组织,检测收集组织中胆盐载体MRP1和MRP2 mRNA的表达。结果ICP和正常妊娠各期胎盘组织中均有MRP2 mRNA的表达,而MRP1 mRNA在大部分标本上有表达;ICP组MRP1 mRNA和MRP2 mRNA表达量与对照组相比(99.94±73.17 vs 99.20±68.65;95.78±56.50 vs 142.20±91.27)差异无统计学意义(P>0.05);ICP组未用地塞米松治疗胎盘MRP2 mRNA表达量低于对照组(91.82±48.08 vs 142.20±91.27,P<0.05)。结论在未用地塞米松治疗的ICP患者胎盘组织中,MRP2 mRNA的表达量降低,这可能是引起ICP患者胎盘胆汁酸转运障碍,从而引起胎儿体内胆汁淤积的机制之一。
