GeneCare Research Institute Co., Ltd., Kamakura, Kanagawa 247-0063, Japan.
Int J Mol Med. 2010 Apr;25(4):537-45. doi: 10.3892/ijmm_00000375.
RecQL1 in the human RecQ DNA helicase family participates in DNA repair and recombination pathways in cell cycle replication. Immunohistochemical analysis of human hepatocellular carcinoma (HCC) tissues showed that RecQL1 expression is strongly correlated with histological grade and MIB-1 indices of HCC, and that the expression was greater in simple HCCs inducing extranodular growth or portal vein invasion than in HCCs not inducing extranodular growth or portal vein invasion. These histological data reveal the potential of RecQL1 as a biological marker predicting the malignancy and progression of liver cancer. High expression profiles were also produced by various HCC cells, including HCC cell lines established by us. When RecQL1 expression was silenced by siRNA in vitro, most HCC cells died of mitotic catastrophe. In a mouse orthotopic xenograft model of liver cancer with transplanted human HCC, RecQL1-siRNA mixed with cationic liposomes exhibited a strong anticancer effect that prevented the growth of the cancer. RecQL1-siRNA inhibited the growth of human HCC in the mouse liver, confirming that RecQL1 is an excellent molecular agent against liver cancer and suggests that RecQL1-siRNA formulated with liver-prone liposomes has excellent potential as a therapeutic drug against liver cancers.
RecQL1 属于人类 RecQ DNA 解旋酶家族，参与细胞周期复制过程中的 DNA 修复和重组途径。对人肝细胞癌 (HCC) 组织的免疫组织化学分析表明，RecQL1 的表达与 HCC 的组织学分级和 MIB-1 指数密切相关，在诱导结节外生长或门静脉侵犯的单纯 HCC 中表达高于不诱导结节外生长或门静脉侵犯的 HCC。这些组织学数据揭示了 RecQL1 作为预测肝癌恶性程度和进展的生物学标志物的潜力。各种 HCC 细胞也表现出高表达谱，包括我们建立的 HCC 细胞系。当 RecQL1 的表达在体外被 siRNA 沉默时，大多数 HCC 细胞死于有丝分裂灾难。在用人 HCC 移植的肝癌小鼠原位异种移植模型中，用阳离子脂质体混合的 RecQL1-siRNA 表现出强烈的抗癌作用，阻止了癌症的生长。RecQL1-siRNA 抑制了人 HCC 在小鼠肝脏中的生长，证实 RecQL1 是一种对抗肝癌的优秀分子药物，并表明用易倾向于肝脏的脂质体配制的 RecQL1-siRNA 作为治疗肝癌的药物具有巨大的潜力。
