New strategy of intravesical in stillation using anti-cancer peptide for bladder tumor

P16是膀胱肿瘤（BT）发生发展的关键分子，通过维持视网膜母细胞瘤蛋白（Rb）的低磷酸化状态来抑制肿瘤生长。在临床样本中，据报道，在约70%的人BT中观察到异常p16。在本研究中，我们研究了新的肽转运蛋白系统是否使用p16的最小抑制序列肽（p16-MIS）的BMP-T可以抑制BT的生长。在体外，肽转移与p16-MIS成功地抑制人和小鼠膀胱肿瘤细胞系与缺乏p16和磷酸化Rb。在体内研究中，局部和全身施用p16-MIS使用BTA-T系统抑制小鼠皮下BT移植物的生长。在组织学检查中，p16-MIS转染降低Rb磷酸化并诱导凋亡。虽然BT膀胱内移植的动物模型尚待建立，但p16-MIS和p16-T联合肽转运蛋白膀胱内灌注可能成为一种新的治疗策略。

P16, which is a key molecule of bladder tumor (BT) development, inhibits the tumor growth through maintaining the retinoblastoma protein (Rb) in its hypophosphorylated state. In clinical samples, it is reported that abnormal p16 was observed in approximately 70% of human BT. In this study, we investigated whether or not new peptide transporter system using Wr-T with minimum inhibitory sequence peptide of p16 (p16-MIS) could inhibit growth of BT. In vitro, peptide transfer with p16-MIS successfully inhibit the human and mouse bladder tumor cell line with absent p16 and phosphorylated Rb. In the in vivo study, both local and systemic administration of p16-MIS using Wr-T system inhibited the growth of subcutaneous BT graft in mice. In histological examination, p16-MIS transfer decreased the Rb phosphorylation and induced the apoptosis. Although animal model for intravesical transplantation of BT should be established, peptide transporter with p16-MIS and Wr-T might become a possible new treatment strategy by intravesical instillation.