Adenovirus-mediated HCCS1 overexpression elicits a potent antitumor efficacy on human colorectal cancer and hepatoma cells both in vitro and in vivo.
We had characterized earlier the novel tumor suppressor gene hepatocellular carcinoma suppressor 1 (HCCS1), and demonstrated that expression of exogenous HCCS1 gene in human hepatocarcinoma cells could remarkably suppress their abilities to develop tumors in nude mice and to form colonies in soft agar. In this study, we provide further experimental evidence to confirm the role of HCCS1 as a tumor suppressor gene and investigate its potential in therapeutic applications by using adenovirus vectors. We show that HCCS1 overexpression, mediated by replication-deficient adenovirus, significantly suppressed the growth of human colorectal cancer cells, as well as hepatocellular carcinoma cells in vitro and in vivo. To further improve its antitumor efficacy, we inserted the HCCS1 gene into an oncolytic adenovirus. This HCCS1-armed oncolytic adenovirus exhibited a dramatic inhibitory effect on cancer cells in vitro and in vivo, and led to a complete regression of 50% of established tumor xenografts in nude mice. Taken together, our data suggest that HCCS1 is a promising therapeutic gene for the treatment of human cancers.
Gan
Y
Y
Laboratory for Cellular and Molecular Immunology, Shanghai Cancer Institute, Shanghai, China.
Gu
J
J
Cai
X
X
Hu
J
J
Liu
X Y
XY
Zhao
X
X
D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000628:therapy*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000628:therapy*; D005822:Genetic Vectors / Q000627:therapeutic use; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D050130:Oncolytic Virotherapy; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D033921:Vesicular Transport Proteins; D023041:Xenograft Model Antitumor Assays
D025521:Tumor Suppressor Proteins; C503307:VPS53 protein, human; D033921:Vesicular Transport Proteins