Tenfibgen-DMAT Nanocapsule Delivers CK2 Inhibitor DMAT to Prostate Cancer Xenograft Tumors Causing Inhibition of Cell Proliferation.
Tenfibgen-DMAT Nanocapsule Delivers CK2 Inhibitor DMAT to Prostate Cancer Xenograft Tumors Causing Inhibition of Cell Proliferation.
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DOI：
10.4255/mcpharmacol.14.02
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发表时间：
2014
期刊：
影响因子：
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通讯作者：
J. Trembley;G. Unger;O. Gomez;J. Abedin;V. Korman;R. Vogel;G. Niehans;B. Kren;K. Ahmed
中科院分区：
文献类型：
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作者：
J. Trembley;G. Unger;O. Gomez;J. Abedin;V. Korman;R. Vogel;G. Niehans;B. Kren;K. Ahmed
CK2是一种主要调节蛋白激酶，在不同的癌症类型中表达增强，被认为是一个有前途的治疗靶点。鉴于CK2信号的普遍表达和对细胞存活的强大影响，肿瘤细胞定向靶向CK2信号是开发抗CK2治疗的重要因素。我们先前报道了一种基于Tbg的纳米胶囊用于在培养的前列腺癌细胞中传递CK2小分子抑制剂2-dimethylamino-4，5，6，7-tetrabromo-1H-benzimidazole(DMAT)的恶性细胞特异性及其对CK2信号的影响。在这里，我们测试了TBG-DMAT对小鼠前列腺癌移植瘤生长的影响。我们的结果表明，TbG-DMAT治疗PC3-LN4移植瘤后，肿瘤中增殖的Ki-67信号和核因子-kappaB(NF-κB)的表达均丢失。此外，在肿瘤中检测到了TBG-DMAT纳米胶囊，而在肝脏和睾丸中没有检测到。总之，基于TBG的抗CK2小分子药物纳米囊给药在前列腺癌的治疗中具有重要的前景。
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-1H-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.