Korang-Yeboah Maxwell, Patel Divya, Morton Derrick, Sharma Pankaj, Gorantla Yamini, Joshi Jugal, Nagappan Perri, Pallaniappan Ravi, Chaudhary Jaideep
College of Pharmacy, Mercer University, Atlanta, GA, USA.
Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA, USA.
Oncotarget. 2016 Oct 18;7(42):68072-68085. doi: 10.18632/oncotarget.10953.
ID4, a helix loop helix transcriptional regulator has emerged as a tumor suppressor in prostate cancer. Epigenetic silencing of ID4 promotes prostate cancer whereas ectopic expression in prostate cancer cell lines blocks cancer phenotype. To directly investigate the anti-tumor property, full length human recombinant ID4 encapsulated in biodegradable Polycaprolactone/Maltodextrin (PCL-MD) nano-carrier was delivered to LNCaP cells in which the native ID4 was stably silenced (LNCaP(-)ID4). The cellular uptake of ID4 resulted in increased apoptosis, decreased proliferation and colony formation. Intratumoral delivery of PCL-MD ID4 into growing LNCaP(-)ID4 tumors in SCID mice significantly reduced the tumor volume compared to the tumors treated with chemotherapeutic Docetaxel. The study supports the feasibility of using nano-carrier encapsulated ID4 protein as a therapeutic. Mechanistically, ID4 may assimilate multiple regulatory pathways for example epigenetic re-programming, integration of multiple AR co-regulators or signaling pathways resulting in tumor suppressor activity of ID4.
ID4是一种螺旋-环-螺旋转录调节因子，已成为前列腺癌中的一种肿瘤抑制因子。ID4的表观遗传沉默促进前列腺癌发生，而在前列腺癌细胞系中的异位表达则可阻断癌症表型。为了直接研究其抗肿瘤特性，将包裹在可生物降解的聚己内酯/麦芽糊精（PCL-MD）纳米载体中的全长人重组ID4递送至LNCaP细胞，该细胞中天然ID4被稳定沉默（LNCaP(-)ID4）。ID4被细胞摄取后导致细胞凋亡增加、增殖减少以及集落形成减少。与用化疗药物多西他赛治疗的肿瘤相比，将PCL-MD ID4瘤内递送至SCID小鼠中生长的LNCaP(-)ID4肿瘤显著减小了肿瘤体积。该研究支持了使用纳米载体包裹的ID4蛋白作为一种治疗方法的可行性。从机制上讲，ID4可能整合多种调节途径，例如表观遗传重编程、多种雄激素受体共调节因子的整合或信号通路，从而产生ID4的肿瘤抑制活性。
