Cancer targeting Gene-Viro-Therapy specific for liver cancer by α-fetoproteincontrolled oncolytic adenovirus expression of SOCS3 and IL-24  

作　　者：Xin Cao Ruicheng Wei Xinran Liu Yan Zeng Hongling Huang Miao Ding Kangjian Zhang Xin-Yuan Liu 

机构地区：[1]Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, ChineseAcademy of Sciences, Shanghai 200031, China [2]Xinyuan Institute of Medicine and Biotechnology, Zhejiang Sci-Tech University, Hangzhou 310018, China [3]Laboratory of Immune Regulation, Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences,Shanghai 200025, China [4]Laboratory of Molecular Virology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200025, China

出　　处：《Acta Biochimica et Biophysica Sinica》2011年第10期813-821,共9页生物化学与生物物理学报（英文版）

摘　　要：The combination of gene therapy and virotherapy for cancer treatment has received close attention and has become a trend in the field of cancer biotherapy. A strat- egy called ＇Cancer Targeting Gene-Viro-Therapy＇ （CTGVT） or ＇Gene Armed Oncolytic Viral Therapy＇ （GAOVT） has been proposed, in which an antitumor gene is inserted into an oncolytic viral vector. In our previous study, a dual-regulated oncolytic adenovirus with enhanced safety for normal cells and strict liver cancertargeting ability, designated AdoenAFPeE1AoE1B （A55） （briefly AdoenAFPeD55）, was successfully constructed. In the current work, interleukin-24 （IL-24） and suppressor of cytokine signaling 3 （SOCS3） genes were packaged into Ad· enAFP · D55. The new constructs, Ad·enAFP·D55（IL-24） and AdeenAFPeD55-（SOCS3）, showed improved tumoricidal activity in hepatoma cell lines compared with the oncolytic viral vector AdeenAFPeD55. The coadministration of Ad · enAFP · D55-（IL-24） and AdoenAFP·D55-（SOCS3） showed much better antitumor effect than Ad·enAFP·D55-（IL-24） or Ad·enAFP·D55- （SOCS3） alone both in vitro and in a nude mouse xenograft model. Moreover, our results also showed that blockade of the Jak/Stat3 pathway by Ad·enAFP·D55- （SOCS3） infection in HUH-7 cells could down-regulate some anti-apoptosis proteins, such as XIAP, Bcl-xL, and survivin, which might sensitize the cells to Ado·nAFP·D55-（IL-24）-induced apoptosis. These results indicate that coadministration of Ad·enAFP·D55-（IL- 24） and Ad·enAFP·D55-（SOCS3） may serve as a candidate therapeutic approach for the treatment of liver cancer.The combination of gene therapy and virotherapy for cancer treatment has received close attention and has become a trend in the field of cancer biotherapy. A strat- egy called ＇Cancer Targeting Gene-Viro-Therapy＇ （CTGVT） or ＇Gene Armed Oncolytic Viral Therapy＇ （GAOVT） has been proposed, in which an antitumor gene is inserted into an oncolytic viral vector. In our previous study, a dual-regulated oncolytic adenovirus with enhanced safety for normal cells and strict liver cancertargeting ability, designated AdoenAFPeE1AoE1B （A55） （briefly AdoenAFPeD55）, was successfully constructed. In the current work, interleukin-24 （IL-24） and suppressor of cytokine signaling 3 （SOCS3） genes were packaged into Ad· enAFP · D55. The new constructs, Ad·enAFP·D55（IL-24） and AdeenAFPeD55-（SOCS3）, showed improved tumoricidal activity in hepatoma cell lines compared with the oncolytic viral vector AdeenAFPeD55. The coadministration of Ad · enAFP · D55-（IL-24） and AdoenAFP·D55-（SOCS3） showed much better antitumor effect than Ad·enAFP·D55-（IL-24） or Ad·enAFP·D55- （SOCS3） alone both in vitro and in a nude mouse xenograft model. Moreover, our results also showed that blockade of the Jak/Stat3 pathway by Ad·enAFP·D55- （SOCS3） infection in HUH-7 cells could down-regulate some anti-apoptosis proteins, such as XIAP, Bcl-xL, and survivin, which might sensitize the cells to Ado·nAFP·D55-（IL-24）-induced apoptosis. These results indicate that coadministration of Ad·enAFP·D55-（IL- 24） and Ad·enAFP·D55-（SOCS3） may serve as a candidate therapeutic approach for the treatment of liver cancer.

关 键 词：cancer biotherapy oncolytic adenovirus APOPTOSIS suppressor of cytokine signaling 3 INTERLEUKIN-24 

分 类 号：Q78[生物学—分子生物学] Q782