PURPOSE: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Oncolytic viruses represent a promising therapeutic agent or vehicle to human cancers due to their ability of selectively lysing cancer cells but not in normal cells. TSLC1, a novel tumor suppressor gene, was loss in many human cancers including HCC, not in normal cells. The current study is focused on the antitumor effect of TSLC1-armed survivin-regulated oncolytic adenovirus for HCC and to explore their molecular mechanism. METHODS: The expression of tumor suppressor TSLC1 and survivin was detected by quantitative PCR. The recombinant virus Ad.SP-E1A-E1B((Δ55))-TSLC1 (brief name as SD55-TSLC1) was constructed by inserting TSLC1 gene into the dual-regulated oncolytic adenovirus vector Ad.SP-E1A-E1B((Δ55)). Then, we performed the antitumor experiments of SD55-TSLC1 in vitro and in nude mice xenografted with Huh7 liver cancer. RESULTS: The expression of TSLC1 was lower in HCC cells than in normal cells, which implied TSLC1 is a tumor suppressor of liver cancer. Survivin expression is higher in detected HCC cells than in normal cells. The SD55-TSLC1 exhibited an excellent antitumor effect on HCC cell growth in vitro but does no or little damage to normal liver cells. Animal experiment further confirmed that SD55-TSLC1 achieved significant inhibition of Huh7 liver cancer xenografted growth. Furthermore, the mechanism of antitumor efficacy by SD55-TSLC1 was elucidated to be due to the activation of caspase apoptotic pathway including the inducement of caspase-3, caspase-8, and poly (ADP-ribose) polymerase cleavage. This is the first report of TSLC1 by oncolytic adenovirus with an excellent antitumor effect to liver cancer growth. CONCLUSION: These data suggest that an oncolytic adenovirus expressing TSLC1 is effective and support that SD55-TSLC1 may be a potent antitumoral agent for future clinical trials of liver cancer.
PURPOSE: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Oncolytic viruses represent a promising therapeutic agent or vehicle to human cancers due to their ability of selectively lysing cancer cells but not in normal cells. TSLC1, a novel tumor suppressor gene, was loss in many human cancers including HCC, not in normal cells. The current study is focused on the antitumor effect of TSLC1-armed survivin-regulated oncolytic adenovirus for HCC and to explore their molecular mechanism. METHODS: The expression of tumor suppressor TSLC1 and survivin was detected by quantitative PCR. The recombinant virus Ad.SP-E1A-E1B((Δ55))-TSLC1 (brief name as SD55-TSLC1) was constructed by inserting TSLC1 gene into the dual-regulated oncolytic adenovirus vector Ad.SP-E1A-E1B((Δ55)). Then, we performed the antitumor experiments of SD55-TSLC1 in vitro and in nude mice xenografted with Huh7 liver cancer. RESULTS: The expression of TSLC1 was lower in HCC cells than in normal cells, which implied TSLC1 is a tumor suppressor of liver cancer. Survivin expression is higher in detected HCC cells than in normal cells. The SD55-TSLC1 exhibited an excellent antitumor effect on HCC cell growth in vitro but does no or little damage to normal liver cells. Animal experiment further confirmed that SD55-TSLC1 achieved significant inhibition of Huh7 liver cancer xenografted growth. Furthermore, the mechanism of antitumor efficacy by SD55-TSLC1 was elucidated to be due to the activation of caspase apoptotic pathway including the inducement of caspase-3, caspase-8, and poly (ADP-ribose) polymerase cleavage. This is the first report of TSLC1 by oncolytic adenovirus with an excellent antitumor effect to liver cancer growth. CONCLUSION: These data suggest that an oncolytic adenovirus expressing TSLC1 is effective and support that SD55-TSLC1 may be a potent antitumoral agent for future clinical trials of liver cancer.
Authors: M Kuramochi; H Fukuhara; T Nobukuni; T Kanbe; T Maruyama; H P Ghosh; M Pletcher; M Isomura; M Onizuka; T Kitamura; T Sekiya; R H Reeves; Y Murakami Journal: Nat Genet Date: 2001-04 Impact factor: 38.330
Authors: Michael J Duffy; Norma O'Donovan; Donal J Brennan; William M Gallagher; Bríd M Ryan Journal: Cancer Lett Date: 2007-02-01 Impact factor: 8.679
Authors: Zi Lai Zhang; Wei Guo Zou; Chun Xia Luo; Bing Hua Li; Jin Hui Wang; Lan Ying Sun; Qi Jun Qian; Xin Yuan Liu Journal: Cell Res Date: 2003-12 Impact factor: 25.617
Authors: Ilya V Ulasov; Zeng B Zhu; Matthew A Tyler; Yu Han; Angel A Rivera; Andrey Khramtsov; David T Curiel; Maciej S Lesniak Journal: Hum Gene Ther Date: 2007-07 Impact factor: 5.695
Authors: Anthony R Prisco; Brian R Hoffmann; Catherine C Kaczorowski; Chris McDermott-Roe; Timothy J Stodola; Eric C Exner; Andrew S Greene Journal: Stem Cells Date: 2016-03-04 Impact factor: 6.277