Dolinsek Tanja, Sersa Gregor, Prosen Lara, Bosnjak Masa, Stimac Monika, Razborsek Urska, Cemazar Maja
Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, SI-1000 Ljubljana, Slovenia.
Faculty of Health Sciences, University of Primorska, Polje 42, SI-6310 Izola, Slovenia.
Cancers (Basel). 2015 Dec 24;8(1):3. doi: 10.3390/cancers8010003.
Endoglin overexpression is associated with highly proliferative tumor endothelium and also with some tumors, including melanoma. Its targeting has anti-tumor effectiveness, which can also be obtained by RNA interference. The aim of our study was to explore the anti-tumor effectiveness of endoglin silencing by electrotransfer of plasmid DNA encoding short hairpin RNA against endoglin in two murine B16 melanoma variants with different metastatic potential on cells, spheroids and subcutaneous tumors in mice. The results demonstrate that endoglin silencing with gene electrotransfer reduces the proliferation, survival and migration of melanoma cells and also has anti-tumor effectiveness, as the therapy resulted in a high percentage of tumor cures (23% and 58% on B16F1 and B16F10 tumors, respectively). The effectiveness of the therapy correlated with endoglin expression in melanoma cells; in vitro the effects were more pronounced in B16F1 cells, which express more endoglin than B16F10. However, the opposite was observed in vivo in tumors, where there was a higher expression of endoglin and better anti-tumor effectiveness in the B16F10 tumor. In conclusion, targeting endoglin for the treatment of melanoma seems to be a concept worthy of further exploration due to the increased therapeutic effect of the therapy based on simultaneous vascular targeting and its direct effect on tumor cells.
内皮糖蛋白的过表达与高度增殖的肿瘤内皮相关，也与包括黑色素瘤在内的一些肿瘤有关。针对内皮糖蛋白的靶向治疗具有抗肿瘤效果，通过RNA干扰也可获得这种效果。我们研究的目的是探讨在两种具有不同转移潜能的小鼠B16黑色素瘤变体的细胞、球体和皮下肿瘤中，通过电转染编码针对内皮糖蛋白的短发夹RNA的质粒DNA来沉默内皮糖蛋白的抗肿瘤效果。结果表明，基因电转染沉默内皮糖蛋白可降低黑色素瘤细胞的增殖、存活和迁移，并且具有抗肿瘤效果，因为该治疗导致了高比例的肿瘤治愈（在B16F1和B16F10肿瘤上分别为23%和58%）。治疗效果与黑色素瘤细胞中的内皮糖蛋白表达相关；在体外，B16F1细胞中的效果更明显，该细胞比B16F10细胞表达更多的内皮糖蛋白。然而，在体内肿瘤中观察到相反的情况，其中B16F10肿瘤中内皮糖蛋白表达更高且抗肿瘤效果更好。总之，由于基于同时进行血管靶向及其对肿瘤细胞的直接作用的治疗具有增强的治疗效果，因此针对内皮糖蛋白治疗黑色素瘤似乎是一个值得进一步探索的概念。
