Vitamin D as a Primer for Oncolytic Viral Therapy in Colon Cancer Models

• Published in: International journal of molecular sciences 2020-10, Vol.21 (19), p.7326
• Main Authors: Kim, Sang-In, Chaurasiya, Shyambabu, Park, Anthony K, Kang, Seonah, Lu, Jianming, Woo, Yanghee, Yin, Hongwei Holly, Yin, Zhirong, Fong, Yuman, Warner, Susanne G
• Format: Article
• Language: English
• Subjects: Alfacalcidol; Animals; Anti-inflammatory agents; Antiviral agents; Apoptosis; Base Sequence - genetics; Calcifediol; Calciferol; Cancer therapies; Cell growth; CF33; Chemotherapy; Colon; Colon cancer; Colonic Neoplasms - genetics; Colonic Neoplasms - immunology; Colonic Neoplasms - therapy; Colonic Neoplasms - virology; Colorectal cancer; Combined Modality Therapy; Cytotoxicity; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; HCT116 Cells; Health aspects; HT29 Cells; Humans; Immunotherapy; Immunotherapy - methods; In vivo methods and tests; Infections; Inflammation; Mice; Oncolysis; Oncolytic Virotherapy; Oncolytic Viruses - genetics; orthopoxvirus; Physiological aspects; Signal transduction; Tumor cell lines; Tumors; Viral infections; virotherapy; Virus Replication - drug effects; Viruses; Vitamin D; Vitamin D - genetics; Vitamin D - pharmacology; Xenograft Model Antitumor Assays; Xenografts; Xenotransplantation
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21197326

Oncolytic viroimmunotherapy is an exciting modality that can offer lasting anti-tumor immunity for aggressive malignancies like colon cancer. The impact of oncolytic viruses may be extended by combining them with agents to prime a tumor for viral susceptibility. This study investigates vitamin D analogue as an adjunct to oncolytic viral therapy for colon cancer. While vitamin D (VD) has historically been viewed as anti-viral, our in vitro investigations using human colon cancer cell lines showed that VD does not directly inhibit replication of recombinant chimeric poxvirus CF33. VD did restrict growth in HT29 but not HCT116 human colon cancer cells. In vivo investigations using HCT116 and HT29 xenograft models of colon cancer demonstrated that a VD analogue, calcipotriol, was additive with CF33-based viral therapy in VD-responsive HT29 but not in HCT116 tumors. Analyses of RNA-sequencing and gene expression data demonstrated a downregulation in the Jak-STAT signaling pathway with the addition of VD to viral therapy in HT29 models suggesting that the anti-inflammatory properties of VD may enhance the effects of viral therapy in some models. In conclusion, VD may prime oncolytic viral therapy in certain colon cancers.