Potent and specific antitumor effect for colorectal cancer by CEA and Rb double regulated oncolytic adenovirus harboring ST13 gene.
Cancer Targeting Gene-Viro-Therapy (CTGVT) is constructed by inserting an antitumor gene into an oncolytic virus (OV). It is actually an OV-gene therapy, which has much better antitumor effect than either gene therapy alone or virotherapy alone in our previously published papers. This study is a modification of CTGVT by inserting a colorectal cancer (CRC) specific suppressor gene, ST13, into a CRC specific oncolytic virus, the Ad·CEA·E1A(Δ24), to construct the Ad·(ST13)·CEA·E1A(Δ24) for increasing the targeting tropism to colorectal cancer and it was briefly named as CTGVT-CRC. Although many studies on CEA promoter and ST13 gene were reported but no construct has been performed to combine both of them as a new strategy for colorectal cancer (CRC) specific therapy. In addition to the CRC specificity, the antitumor effect of Ad·(ST13)·CEA·E1A(Δ24) was also excellent and got nearly complete inhibition (not eradication) of CRC xenograft since ST13 was an effective antitumor gene with less toxicity, and a Chinese patent (No. 201110319434.4) was available for this study. Ad·(ST13)·CEA·E1A(Δ24) caused cell apoptosis through P38 MAPK (i.e. P38) which upregulated CHOP and ATF2 expression. The mitochondrial medicated apoptosis pathway was activated by the increase of caspase 9 and caspase 3 expression.
Xinyuan Institute of Medicine and Biotechnology, College of Life Science, Zhejiang Sci-Tech University, Hangzhou, China.
Xiumei
X
Zhou
Guoliang
G
Xie
Shibing
S
Wang
Yigang
Y
Wang
Kangjian
K
Zhang
Shu
S
Zheng
Liang
L
Chu
Lianli
L
Xiao
Yuemei
Y
Yu
Yue
Y
Zhang
Xinyuan
X
Liu
D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000235:genetics / Q000627:therapeutic use; D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics*; D014183:Transplantation, Heterologous; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000627:therapeutic use; D018832:Molecular Chaperones
D002352:Carrier Proteins; D025521:Tumor Suppressor Proteins; C101119:ST13 protein, human; D018832:Molecular Chaperones