靶向中期因子反义寡核苷酸的体内抗肿瘤双应

目的 观察靶向中期因子反义寡核苷酸的体内抗肿瘤效应.方法 构建人肝癌裸鼠原位移植瘤模型48只,随机分6组,生理盐水对照组,MK-AS(每日25、50、100mg/kg)组,MK-Sen(每日50mg/kg)组和5-Fu(每日10 mg/kg)组,放免法检测血清AFP浓度,Western blot检测组织MK、p53、bax、bcl-2和Caspase-3蛋白水平.结果 (1)与生理盐水对照组比较,MK-AS治疗组的肿瘤体积明显减小,[(807.75±195.19)mm3比(552.75±84.38)、(532.00±121.57)、(294.50±70.66)mm3],差异有统计学意义(P<0.01);(2)MK.AS治疗组的肿瘤瘤重与生理盐水对照组比较显著降低,[(1.29±0.13)g比(0.70±0.14)、(0.64±0.18)和(0.44±0.18)g],差异有统计学意义(P<0.01);(3)MK-AS明显下调肿瘤组织MK和bcl-2蛋白的表达,而p53、bax、Caspase-3表达上调.结论 MK-AS具有明显的体内抗肿瘤效应;MK-AS的抗肿瘤效应可能与凋亡相关蛋白p53、bax、Caspase-3表达水平的上调和bcl-2的下调有关.

Antitumor effects of antisense oligonucleotides targeting midkine in vivo

Objective To evaluate the in vivo entitumor effects of antiseuse oligonucleotides targe-ting midkine (MK-AS). Methods An in situ human hepatecellular carcinoma (HCC) model was estab-fetpprotein (AFP) were measured by calipers and radiation immunoassay relatively. Morphology of tumors was evaluated by hematoxylin-eosin(H&E) staining of histological sections. Human midkine(MK), p53, bax, bcl-2 and Caspase-3 protein contents were detected by Western blotting. Results MK-AS significantly inhibited in situ human HCC growth in mice compared to the saline group in tumor volume and weight. The tumor volume of mice injected by intravenously with saline (vehicle control),MK-AS with 25,50 and 100 spectively, and the tumor volumes were decreased in the MK-AS treatment group compared to the saline con-trol group (all P<0.01). The tumor weights were (1.29±0.13), (0.70 s 0.14), (0.64±0.18), and (0.44±0.18) g respectively,and the tumor weights were decreased in the MK-AS treatment group com-pared to the saline control group (P<0.01). Interestingly, MK-AS also clearly down-regulated the protein level of bcl-2, and up-regulated p53, bax and Caspase-3 in the hepatecellular carcinoma tissues. Conclu-sion MK-AS was an effective antitumor antisense oligonucleotide in vivo,and its antitumor effect was as-sociated with the increase of proapoptotic proteins, such as p53, bax and Caspase-3, and the decrease of an-tiapoptotie protein bcl-2.