Antitumor activity of an adenovirus harboring human IL-24 in colon cancer.
Data have increasingly shown that melanoma differentiation associated gene-7 (Mda-7/IL-24) has growth suppression activity and can induce apoptosis in many tumor cells, but to our knowledge there have been few studies about its role in colon cancer. We examined its anti-cancer effect on colon cancer. We constructed a recombinant replication-deficient adenovirus carrying human melanoma differentiation associated gene-7 (Ad-IL-24) and examined its apoptosis-inducing efficacy on the colon cancer HT-29 cell line and on an oxaliplatin-resistant cell line HT-29/oxa, using a combination of flow cytometry, growth suppressive activity by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and xenografts. Furthermore, we tested the suppression activity of Mda-7/IL-24 on vascular endothelial growth factor (VEGF) and microvessel density (MVD), as well as the inductive effect on expression of the growth arrest and DNA damage gene (GADD) in xenograft tumors by immunohistochemistry. Melanoma differentiation associated gene-7 can inhibit the growth of colon cancer cell lines and induced apoptosis in about (5.6±0.3)% of HT-29 cells (P<0.05). Xenograft growth was retarded in vivo in mice treated with melanoma differentiation associated gene-7, but the tumor proliferation rate for this group was not significantly different in comparison to controls (P>0.05). Furthermore, melanoma differentiation associated gene-7 induced expression of a growth arrest and DNA damage (GADD) gene and reduced the expression of both VEGF and MVD in xenograft tumors. This study supports a potential therapeutic effect for melanoma differentiation associated gene-7 on colon cancer.
Chang
Shujian
S
Department of Oncology, The Fourth Affiliated Hospital, Soochow University, Wuxi, 214062, China. changsj88265@sina.com
Yang
Jicheng
J
Chen
Weichang
W
Xie
Yufeng
Y
Sheng
Weihua
W
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000098:blood supply / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000150:complications / Q000188:drug therapy; D009944:Organoplatinum Compounds / Q000494:pharmacology / Q000627:therapeutic use; D000077150:Oxaliplatin; D014161:Transduction, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D000099180:Interleukin-24
D049452:Green Fluorescent Proteins; D007378:Interleukins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D042461:Vascular Endothelial Growth Factor A; D000099180:Interleukin-24