目的 探究超声-微泡介导的miR-128通过调节PTEN对乳腺癌细胞阿霉素耐药的影响。方法 qPCR检测miR-128在乳腺癌细胞系中的表达,并利用结合微泡的miR-128质粒(质粒+超声+SF6微泡)转染细胞,探究超声-微泡介导的miR-128对乳腺癌细胞阿霉素耐药的影响。CCK8实验检测乳腺癌细胞的活性;qPCR检测过表达miR-128后对PTEN的影响和对乳腺癌细胞阿霉素耐药的影响。结果 miR-128在阿霉素耐药乳腺癌细胞中低表达;过表达miR-128能够增加乳腺癌细胞对阿霉素的敏感性,超声-微泡介导的miR-128进一步增强了乳腺癌细胞对阿霉素的敏感性;miR-128通过调节PTEN从而促进乳腺癌细胞对阿霉素耐药。结论 miR-128过表达可以增强乳腺癌对阿霉素的敏感性,超声-微泡介导的miR-128进一步增强了乳腺癌细胞对阿霉素的敏感性,本研究为乳腺癌阿霉素耐药的治疗提供了新的分子靶标和治疗途径。
Objective To explore the effect of ultrasound-microbubble mediated miR-128 on doxorubicin resistance in breast cancer cells by regulating PTEN. Methods Quantitatine PCR (qPCR) was used to detect the expression of miR-128 in breast cancer cell lines, and the ultrasound-microbubble combined miR-128 plasmid(plasmid+ultrasound+SF6 microbubbles) was used to transfect the cells to explore the effects of ultrasound-microbubble mediated miR-128 on doxorubicin resistance in cancer cells. The CCK8 experiment was used to detect the activity of breast cancer cells; qPCR was used to detect the effect of overexpression of miR-128 on PTEN and the effect on doxorubicin resistance of breast cancer cells. Results miR-128 was under-expressed in doxorubicin-resistant breast cancer cells; overexpression of miR-128 increased the sensitivity of breast cancer cells to doxorubicin,ultrasound-microbubble mediated miR-128 further enhanced breast cancer cells sensitivity to doxorubicin; miR-128 promote resistance to doxorubicin in breast cancer cells by regulating PTEN. Conclusion Overexpression of miR-128 could enhance the sensitivity of breast cancer to doxorubicin. Ultrasound-microbubble mediated miR-128 further enhanced the sensitivity. This study provided a treatment for doxorubicin resistance in breast cancer with new molecular targets and therapeutic approaches.
目的 研究雷公藤红素对人阿霉素耐药MCF-7/ADR乳腺癌细胞生长的作用。方法 采用MTT试验检测MCF-7/ADR细胞对阿霉素的耐药情况以及雷公藤红素对MCF-7/ADR细胞生长的影响;采用Annexin V-FITC/PI双染试验分析雷公藤红素对MCF-7/ADR耐药细胞凋亡的诱导作用;应用流式细胞周期分析检测雷公藤红素对MCF-7/ADR耐药细胞周期的影响。结果 MCF-7/ADR细胞对阿霉素耐药指数达14.54;而雷公藤红素能有效抑制阿霉素耐药细胞MCF-7/ADR的生长,并呈现浓度依赖性,作用48 h的IC50是1.04 μmol/L,MCF-7/ADR对雷公藤红素的耐药指数仅为0.87。2 μmol/L雷公藤红素作用8 h后,Annexin V-FITC染色阳性的MCF-7/ADR细胞比例较对照显著升高,差异有统计学意义(P＜0.05)。在1 μmol/L雷公藤红素作用24 h后,G1期细胞比例由对照(59.22±3.78)%升高至(77.44±4.21)%,而S期细胞比例由对照(37.51±2.91)%降至(19.65±2.25)%,差异有统计学意义(P＜0.05)。结论 雷公藤红素能激活MCF-7/ADR细胞凋亡的发生,并诱导MCF-7/ADR发生 G1/S细胞周期阻滞,从而对阿霉素耐药MCF-7/ADR细胞的生长发挥高效抑制作用。
Objective To investigate the effect of celastrol on the growth of adriamycin-resistant MCF-7/ADR breast cancer cells. Methods The resistance situation of MCF-7/ADR cells to adriamycin and the effect of celastrol on the growth of adriamycin-resistant MCF-7/ADR cells were evaluated by MTT assay. The effect of celastrol on apoptosis in MCF-7/ADR breast cancer cells was determined by annexin V-FITC/PI double staining. The effect of celastrol on cell cycle progression was determined by flow cytometry analysis. Results The resistance index of MCF-7/ADR cells to adriamycin was 14.54. After treatment with celastrol for 48 h, MCF-7/ADR cells displayed markedly inhibited growth in a dose-dependent manner, and calculated IC50 was 1.04 μmol/L. Celastrol decreased the resistance index of MCF-7/ADR from 14.54 to 0.87. The numbers of apoptotic MCF-7/ADR cells, as revealed by annexin V binding, significantly increased upon celastrol treatment (P＜0.05). Celastrol treatment caused an increase of cells in G1 phase from (59.22±3.78)% to (77.44±4.21)%, while the percentage of cells in S phase was decreased from(37.51±2.91)% to(19.65±2.25)%(P＜0.05). Conclusion These data demonstrated that celastrol induced apoptosis and G1/S cell cycle arrest in MCF-7/ADR cells and consequently displayed potent cytocidal effect on adriamycin-resistant MCF-7/ADR breast cancer cells.
目的 初步探讨可注射型载阿霉素水凝胶对胶质瘤的治疗作用。方法 使用透析法检测载阿霉素水凝胶在体外释放药物的情况。构建大鼠皮下C6胶质瘤模型，按不同给药途径分为空白对照组、经静脉注射组、水凝胶组。给药15 h后，经免疫荧光检测阿霉素在肿瘤内部的分布情况。给药7 d后，计算出各组的抑瘤率；并对肿瘤组织进行苏木精-伊红染色。结果 在体外，载阿霉素水凝胶具有缓释药物的性能。在体内，与经静脉给药相比，局部注射载阿霉素水凝胶使瘤内分布更多阿霉素，抑瘤率更高（42% vs 64%），肿瘤细胞坏死更明显。结论 载阿霉素水凝胶可为胶质瘤局部化学治提供新的载体。
Objective To investigate the therapeutic effect of injectable doxorubicin-containing hydrogel on glioma．Methods The release of doxorubicin hydrogel in vitro was detected by dialysis．The subcutaneous C6 glioma model of rats was constructed and divided into blank control group，intravenous injection group and hydrogel group according to different administration methods．The distribution of doxorubicin in the tumor was detected by immunofluorescence 15 hours after administration．After 7 days of administration，the tumor inhibition rate of each group was calculated．The tumor tissue was stained with hematoxylin eosin．Results In vitro，doxorubicin-containing hydrogels had sustained drug release properties．In vivo，compared with intravenous administration，local injection of doxorubicin-containing hydrogel resulted in more doxorubicin distribution，higher tumor inhibition rate（42% vs 64%）and more obvious tumor cell necrosis．Conclusions Doxorubicin-containing hydrogel can provide a new carrierfor local chemotherapy of glioma．
