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

P16是膀胱肿瘤（BT）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的生长。在临床样本中，有报道称大约70%的人BT中存在异常的p16，在本研究中，我们研究了含有p16最小抑制序列肽的Wr-T （p16- mis）的新肽转运体系统是否能抑制BT的生长，在体外，p16- mis的肽转移成功地抑制了p16缺失和磷酸化Rb的人和小鼠膀胱肿瘤细胞系。在体内研究中，使用Wr-T系统局部和全身给药p16-MIS均能抑制小鼠皮下BT移植物的生长。组织学检查显示，p16-MIS的转移降低了Rb磷酸化，诱导了细胞凋亡。虽然需要建立BT膀胱内移植动物模型，但p16-MIS和Wr-T的肽转运体可能成为膀胱内灌注治疗BT的新策略。

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.