Trembley Janeen H, Unger Gretchen M, Gomez Omar Cespedes, Abedin J, Korman Vicci L, Vogel Rachel I, Niehans Gloria, Kren Betsy T, Ahmed Khalil
Research Service, Minneapolis VA Health Care System, Minneapolis ; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis ; Masonic Cancer Center, University of Minnesota, Minneapolis.
GeneSegues Inc., Chaska, Minnesota.
Mol Cell Pharmacol. 2014;6(2):15-25.
CK2 is a master regulator protein kinase which demonstrates heightened expression in diverse cancer types and is considered a promising target for therapy. Given its ubiquitous expression and potent influence on cell survival, cancer cell-directed targeting of the CK2 signal is an important factor for development of an anti-CK2 therapeutic. We previously reported on the malignant cell specificity and effect on CK2 signaling of a tenfibgen (TBG) based nanocapsule for delivery of the CK2 small molecule inhibitor 2-dimethylamino-4,5,6,7-tetrabromo-1-benzimidazole (DMAT) in cultured prostate cancer cells. Here we tested the ability of TBG-DMAT to affect the growth of prostate xenograft tumors in mice. Our results show that treatment of PC3-LN4 xenograft tumors with TBG-DMAT caused loss of proliferative Ki-67 signal as well as Nuclear Factor-kappa B (NF-κB) expression in the tumors. Further, the TBG-DMAT nanocapsule was detected in tumors and not in liver or testis. In conclusion, TBG-based nanocapsule delivery of anti-CK2 small molecule drugs holds significant promise for treatment of prostate cancer.
CK2是一种主要的调节蛋白激酶，在多种癌症类型中表达上调，被认为是一个有前景的治疗靶点。鉴于其广泛表达以及对细胞存活的强大影响，针对癌细胞靶向CK2信号是开发抗CK2疗法的一个重要因素。我们之前报道了一种基于腱生蛋白（TBG）的纳米胶囊对CK2小分子抑制剂2-二甲基氨基-4,5,6,7-四溴-1-苯并咪唑（DMAT）的恶性细胞特异性及其对培养的前列腺癌细胞中CK2信号的影响。在此，我们测试了TBG-DMAT影响小鼠前列腺异种移植瘤生长的能力。我们的结果表明，用TBG-DMAT处理PC3-LN4异种移植瘤会导致肿瘤中增殖性Ki-67信号以及核因子κB（NF-κB）表达丧失。此外，在肿瘤中检测到了TBG-DMAT纳米胶囊，而在肝脏或睾丸中未检测到。总之，基于TBG的纳米胶囊递送抗CK2小分子药物在前列腺癌治疗方面具有重大前景。
