miR-21反义寡核苷酸联合顺铂对裸鼠骨肉瘤生长的抑制

摘要

Objective To explore the effects of miR-21 antisense oligonucleotides(ASO)and cisplatin combined on the growth of subcutaneous xenotransplanted osteosarcomas in nude mice.Methods Xenotransplanted osteosarcoma models were established in nude mice by injection of human osteosarcoma cells MG-63.Inoculated mice were randomly divided into four groups(blank control group,cisplatin group,anti-miR-21 group,anti-miR-21+cisplatin group).The rats were treated by injec-tion of anti-miR-21 into the tumors in anti-miR-21 group,by injection of cisplatin through tail veins in cisplatin group or by in-jection both of them in anti-miR-21+ cisplatin group.The volume and weight of tumors were measured and the inhibition rates of tumors were calculated on a daily basis.Meanwhile,MG-63 cells were divided into the same four groups as mentioned be-fore.The cell proliferation was detected by MTT assay and the cell apoptosis by Annexin V analysis.Results The inhibition of tumor growth(volume and weight)was obvious in the anti-miR-21+cisplatin group compared to the control groups.In vitro cell growth was significantly inhibited and cell apoptosis increased obviously in the anti-miR-21 + cisplatin group compared to the control groups(P <0.05).Conclusion MiR-21 ASO combined with cisplatin can inhibit cell proliferation,promote cell apopto-sis in vitro ,and obviously suppress tumor growth in vivo.They may be used to treat osteosarcoma.%目的 探讨miR-21反义寡核苷酸(anti-miR-21)联合顺铂对人骨肉瘤裸鼠皮下移植瘤的作用.方法 将人骨肉瘤MG-63细胞株接种于裸鼠皮下,建立骨肉瘤裸鼠模型,并将裸鼠随机分为4组(对照组、顺铂组、anti-miR-21组、an-ti-miR-21+顺铂组),anti-miR-21采用瘤内直接注射、顺铂采用尾静脉注射,每日称量裸鼠体重、测量瘤体体积及取瘤后称量瘤体重量,并计算抑瘤率;体外实验将MG-63细胞分为对照组、顺铂组、anti-miR-21组、anti-miR-21+顺铂组,分组处理后用MTT法检测转染后细胞体外的增殖情况,用流式细胞术检测细胞凋亡情况.结果 经anti-miR-21联合顺铂治疗的肿瘤生长较对照明显要慢,且无论是在重量和体积上都与顺铂组有显著性差异.体外经anti-miR-21联合顺铂处理的肿瘤细胞增殖受到显著抑制,凋亡率明显增高,与顺铂组比较差异均具有统计学意义.结论 miR-21反义寡核苷酸联合顺铂在体外能显著抑制细胞生长、促进细胞凋亡;在体内能明显地抑制肿瘤生长,对人骨肉瘤裸鼠移植瘤具有一定的治疗作用.