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肿瘤的多药耐药是肿瘤化疗失败的主要原因,由于载有柔红霉素的磁性纳米Fe3O4颗粒在体外显示了良好的耐药逆转效果,本实验研究了载有柔红霉素的磁性纳米Fe3O4颗粒在体内对白血病多药耐药逆转效果。将裸鼠高成瘤性白血病细胞株K562-n及其相应的多药耐药株K562-n/VCR分别接种于裸鼠的两侧腹股沟皮下,以建立人类白血病移植瘤模型;将双侧成瘤裸鼠随机分为5组,A组给予生理盐水,B组给予磁性纳米Fe3O4颗粒,C组给予柔红霉素,D组给予载有柔红霉素的磁性纳米Fe3O4颗粒,E组给予载有柔红霉素的磁性纳米Fe3O4颗粒同时在肿瘤表面建立固定磁场。在实验开始后的第1,5,9,13,17,21天分别测量肿瘤体积。实验结束后,分离瘤组织并用RT-PCR,Westernblot检测mdr-1的转录和表达。结果表明:D组、E组的K562-n/VCR肿瘤体积显著小于A、B、C3个组(D或E组相对于A,B或C组p<0.05)。病理检查显示:A组、B组肿瘤细胞生长良好,未见明显细胞坏死;C组肿瘤细胞有散在细胞坏死,部分细胞出现核固缩、核碎裂等;D、E组肿瘤组织内可见细胞明显破碎、坏死、组织的纤维化。D和E组的mdr-1的转录水平明显低于A、B、C3个组,但是P-gp的表达在5个组中无差异。C组、D组、E组3个组K562-n肿瘤平均肿瘤体积显著小于的A、B两组的平均肿瘤体积(C、D或E组相对于A或B组p<0.05)。A组、B组肿瘤细胞生长良好,未见明显细胞坏死;在C、D、E组肿瘤组织内可见细胞明显破碎、坏死、组织的纤维化。结论:载有柔红霉素的磁性纳米Fe3O4颗粒在体内具有明显的逆转多药耐药的作用,但是相对于单用柔红霉素,载有柔红霉素的磁性纳米Fe3O4颗粒在敏感的K562-n的肿瘤中并不能进一步提高疗效;本实验中外加磁场并未增加疗效。
The multidrug resistance of tumor is the main reason of tumor chemotherapy failure. Since the magnetic nano-Fe3O4 particles containing daunorubicin have a good drug-resistant reversal effect in vitro, the present study investigated the effect of daunorubicin- Fe3O4 particles in vivo reversal of multidrug resistance of leukemia. The nude mouse model of high-neoplastic leukemia cell line K562-n and its corresponding multidrug-resistant K562-n / VCR were inoculated subcutaneously into the groin on both sides of nude mice to establish a human leukemia xenograft model. The nude mice were randomly divided into five groups: group A received normal saline, group B received magnetic nano-Fe3O4 particles, group C received daunorubicin, group D received daunorubicin-loaded magnetic nano-Fe3O4 particles, A daunorubicin magnetic nano-Fe3O4 particles at the same time in the tumor surface to establish a fixed magnetic field. Tumor volume was measured on days 1, 5, 9, 13, 17 and 21 after the start of the experiment. After the experiment, the tumor tissues were isolated and the transcription and expression of mdr-1 were detected by RT-PCR and Western blot. The results showed that the tumor volumes of K562-n / VCR in group D and group E were significantly smaller than those in group A, B and C3 (p <0.05 for group D or E compared to group A, B or C). Pathological examination showed that the tumor cells in group A and group B grew well, and no obvious cell necrosis was observed. In group C, scattered necrotic cells were observed in tumor cells, and nuclear pyknosis and nuclear fragmentation were observed in some cells. In group D and group E, Obviously broken, necrosis, tissue fibrosis. The transcriptional levels of mdr-1 in groups D and E were significantly lower than those in groups A, B and C3, but there was no difference in the expression of P-gp among the five groups. The mean tumor volume of K562-n tumors in group C, group D and group E was significantly less than that in group A and B (p <0.05 for group C, D or E versus group A or B). The tumor cells in group A and group B grew well, and no obvious cell necrosis was observed. In group C, D and E, the cells were obviously broken, necrotic and the fibrosis of tissues. CONCLUSION: The magnetic nano-Fe3O4 particles containing daunorubicin have a significant reversal effect on multidrug resistance in vivo, but compared with daunorubicin alone, the magnetic nano-Fe3O4 particles containing daunorubicin are sensitive to K562-n in the tumor and can not further improve the efficacy; In this experiment did not increase the magnetic field effect.