State Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, The Chinese Academy of Sciences, China.
Cancer Gene Ther. 2012 Sep;19(9):619-29. doi: 10.1038/cgt.2012.40. Epub 2012 Jul 13.
Interleukin (IL)-24, a promising therapeutic gene, has been widely used for Cancer Targeting Gene-Viro-Therapy (CTGVT). In this study, IL-24 was inserted into an oncolytic adenovirus in which the E1A gene is driven by an enhanced, short α-fetoprotein (AFP) promoter and the E1B gene is completely deleted to form Ad.enAFP-E1A-ΔE1B-IL-24. This construct has a potent antitumor effect on liver cancer cell lines in vitro, but little or no effect on normal cell lines, such as L-02 and QSG-7701. In vivo, the complete elimination of Huh-7 liver cancer in nude mice with Ad.enAFP-E1A-ΔE1B-IL-24 intratumor injection was observed. The design of Ad.enAFP-E1A-ΔE1B-IL-24 and its potent antitumor effect on liver cancer have not been published previously. The mechanism of the potent antitumor effect of Ad.enAFP-E1A-ΔE1B-IL-24 is due to the upregulation of GADD34 and intrinsic and extrinsic apoptotic signaling.
白细胞介素（IL）-24 是一种很有前途的治疗基因，已被广泛用于癌症靶向基因-病毒治疗（CTGVT）。在本研究中，IL-24 被插入一种溶瘤腺病毒中，其中 E1A 基因由增强的短α-胎蛋白（AFP）启动子驱动，E1B 基因完全缺失，形成 Ad.enAFP-E1A-ΔE1B-IL-24。该构建体在体外对肝癌细胞系具有很强的抗肿瘤作用，但对正常细胞系，如 L-02 和 QSG-7701，几乎没有或没有作用。在体内，用 Ad.enAFP-E1A-ΔE1B-IL-24 瘤内注射完全消除了裸鼠的 Huh-7 肝癌。Ad.enAFP-E1A-ΔE1B-IL-24 的设计及其对肝癌的强大抗肿瘤作用以前没有发表过。Ad.enAFP-E1A-ΔE1B-IL-24 强大抗肿瘤作用的机制是由于 GADD34 的上调以及内在和外在的凋亡信号。
