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Published on: July 30, 2018
Antitumor activity of an adenovirus harboring human IL-24 in colon cancer
Shujian Chang1, Jicheng Yang, Weichang Chen
1Department of Oncology, The Fourth Affiliated Hospital, Soochow University, Wuxi, 214062, China. changsj88265@sina.com
Abstract:
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.
Insights
Melanoma differentiation associated gene-7 (Mda-7/IL-24) shows potential as a colon cancer therapy. It inhibits colon cancer cell growth, induces apoptosis, and reduces tumor vascularization in preclinical models.
Area of Science:
- Oncology
- Molecular Biology
- Gene Therapy
Background:
- Melanoma differentiation associated gene-7 (Mda-7/IL-24) exhibits anti-tumor properties in various cancer types.
- Its therapeutic role in colon cancer, particularly in oxaliplatin-resistant models, remains largely unexplored.
Purpose of the Study:
- To investigate the anti-cancer effects of Mda-7/IL-24 on colon cancer cell lines and xenografts.
- To assess Mda-7/IL-24's impact on apoptosis, cell proliferation, vascular endothelial growth factor (VEGF), and microvessel density (MVD).
Main Methods:
- Construction of a recombinant replication-deficient adenovirus carrying human Mda-7/IL-24 (Ad-IL-24).
- Evaluation of apoptosis and growth suppression using flow cytometry and MTT assays in HT-29 and HT-29/oxa colon cancer cells.
- In vivo assessment using xenograft models, including immunohistochemical analysis of VEGF, MVD, and growth arrest and DNA damage (GADD) gene expression.
Main Results:
- Ad-IL-24 treatment induced apoptosis in HT-29 cells (5.6±0.3%) and inhibited colon cancer cell growth.
- Xenograft tumor growth was retarded in vivo, although proliferation rates were not significantly different from controls.
- Mda-7/IL-24 upregulated GADD gene expression and downregulated VEGF and MVD in xenograft tumors.
Conclusions:
- Mda-7/IL-24 demonstrates significant anti-cancer activity against colon cancer, including oxaliplatin-resistant cells.
- The gene therapy approach shows promise by inducing apoptosis and inhibiting tumor angiogenesis.
- Further research into Mda-7/IL-24 as a therapeutic agent for colon cancer is warranted.
