Sun Miaonan, Sun Liankun, Sun Dejun, Zhang Chunmei, Li Mei
1Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, 130021 China.
2Department of Biomedicine, Regeneration Medicine Institute, College of Pharmacy, Jilin University, Changchun, 130021 China.
Cancer Cell Int. 2018 Apr 16;18:58. doi: 10.1186/s12935-018-0546-7. eCollection 2018.
Immunotoxins are typical therapeutic drugs that can target cancer cells. They exploit the affinity of specific monoclonal antibodies or ligands to cancer cells to deliver a conjugated protein toxin to target sites, thus, attacking the cancer cells.
The immuno-RNase, Onc-V3, showed the stability of Onc-V3 in the blood stream. Flow cytometry showed that apoptosis occurred in the HO-8910PM cells when treated with Onc-V3. Under the confocal microscope, the green fluorescent, FITC-Onc-V3, were located in the cytoplasm, suggesting that Onc-V3 had a function in the cytoplasm of cancer cells. Moreover, after staining by DAPI, the blue fluorescent nuclei showed shrinkage and grainy. Wound healing assay showed that high concentrations of Onc-V3 inhibited cell migration and the transwell invasion assay showed that Onc-V3 could inhibit cell invasion to the basement membrane. Western blot results showed significantly decreased PARP, procaspase-9, and procaspase-3 in Onc-V3-induced apoptosis.
These results of the experiments in vitro had shown that the Onc-V3 could be delivered to the cancer cells accurately and it had strong cytotoxicity on high metastatic cancer cells.
The specific toxicity of Onc-V3 on highly metastatic cancer cells can make it a promising anti-cancer drug by using V3 to target delivery of Onconase.
免疫毒素是一类典型的可靶向癌细胞的治疗药物。它们利用特异性单克隆抗体或配体与癌细胞的亲和力,将结合的蛋白毒素递送至靶位点,从而攻击癌细胞。
免疫核糖核酸酶Onc-V3在血流中表现出稳定性。流式细胞术显示,用Onc-V3处理HO-8910PM细胞时会发生凋亡。在共聚焦显微镜下,绿色荧光的FITC-Onc-V3位于细胞质中,表明Onc-V3在癌细胞细胞质中发挥作用。此外,经DAPI染色后,蓝色荧光细胞核出现萎缩且呈颗粒状。伤口愈合试验表明,高浓度的Onc-V3抑制细胞迁移,而Transwell侵袭试验表明Onc-V3可抑制细胞向基底膜的侵袭。蛋白质免疫印迹结果显示,Onc-V3诱导的凋亡中PARP、procaspase-9和procaspase-3显著减少。
这些体外实验结果表明,Onc-V3可准确递送至癌细胞,对高转移性癌细胞具有强大的细胞毒性。
Onc-V3对高转移性癌细胞的特异性毒性使其有望成为一种通过利用V3靶向递送昂卡酶的抗癌药物。