tenfigen -DMAT纳米胶囊向前列腺癌异种移植肿瘤递送CK2抑制剂DMAT,抑制细胞增殖。

J. Trembley, G. Unger, O. Gomez, J. Abedin, V. Korman, R. Vogel, G. Niehans, B. Kren, K. Ahmed
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引用次数: 13

摘要

CK2是一种主调控蛋白激酶,在多种癌症类型中表达升高,被认为是一种有希望的治疗靶点。鉴于其无处不在的表达和对细胞存活的强大影响,癌细胞定向靶向CK2信号是开发抗CK2治疗药物的重要因素。我们之前报道了一种基于tenfibren (TBG)的纳米胶囊在培养的前列腺癌细胞中递送CK2小分子抑制剂2-二甲氨基-4,5,6,7-四溴-1 -苯并咪唑(dmatt)的恶性细胞特异性和对CK2信号传导的影响。在这里,我们测试了TBG-DMAT对小鼠前列腺异种移植肿瘤生长的影响。我们的研究结果表明,TBG-DMAT治疗PC3-LN4异种移植肿瘤可导致肿瘤中增殖性Ki-67信号和核因子κB (NF-κB)表达的丧失。此外,TBG-DMAT纳米胶囊在肿瘤中检测到,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的治疗中具有重要的前景。
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Tenfibgen-DMAT Nanocapsule Delivers CK2 Inhibitor DMAT to Prostate Cancer Xenograft Tumors Causing Inhibition of Cell Proliferation.
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.
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