Effect of adoptive t cell therapy on vegf signaling pathway in dmh-induced colon cancer in balb/c mice
Loading...
Date
Journal Title
Journal ISSN
Volume Title
Publisher
Medical Project Poland
Abstract
Colon cancer is the fourth most leading causes of cancer-related deaths worldwide accounting for nearly 7-10% of all cancers. Adoptive T Cell Therapy (ACT), a type of immunotherapy, was first developed using Tumor-Infiltrating Lymphocytes (TILs) whereby TILs from the cancer patients are isolated, expanded in vitro using a high concentration of Interleukin-2 (IL-2), and then injected back into the same patients. It was shown that chemotherapy-induced lymphodepletion prior to ACT activates the persistence and anticancer effectiveness of the injected cells. In this study, we aimed to determine the effect of Adoptive T cell therapy (CD8 T cell therapy) alone or in adjunct to Sorafenib on the Vascular Endothelial Growth Factor (VEGF) signaling pathway. CRC was induced in Balb/c mice using dimethylhydrazine injections once per week for 12 consecutive weeks. The mice were treated with either sorafenib, Adoptive T cell therapy or both. Colons were used for histological and molecular analysis. Gene expression was performed using RT-PCR. Sorafenib and/or Adoptive T cell therapy aided in restoring the normal histology and structure of colon cancer tissue. Sorafenib and/or CD8 T cell treatment led to a decrease in the expression levels of VEGF-A, VEGFR-1, VEGFR-2, BRAF, mTOR, PI3K, KRAS and AKT as compared to untreated control Balb/c mice group. In conclusion, our findings may open up future work on the effect CD8 T cell therapy in colon cancer and on producing new anti-colon cancer therapeutic agents targeting these pathways. This study may be utilized as a base for immunotherapeutic research in colon cancer. © Oncology and Radiotherapy.
Description
Keywords
Adoptive immunotherapy, Chemotherapy, Colon cancer, Vegf/ vegfr, 1,2 dimethylhydrazine, Agarose, Alcohol, B raf kinase, Buffer, Cd19 antigen, Cd28 antigen, Cd3 antigen, Cd4 antibody, Cd8 antigen, Complementary dna, Cyanine dye 5, Deoxyribonuclease, Dimethyl sulfoxide, Dimethylhydrazine, Eosin, Ethidium bromide, Fluorescein isothiocyanate, Formaldehyde, Genomic dna, Glutamine, Glyceraldehyde 3 phosphate dehydrogenase, Hematoxylin, Interleukin 2, Interleukin 7, K ras protein, Mammalian target of rapamycin, Mercaptoethanol, Penicillin derivative, Phosphate buffered saline, Phosphatidylinositol 3 kinase, Ribonuclease, Rna 18s, Rna 28s, Rna directed dna polymerase, Sorafenib, Sterile water, Streptomycin, Vasculotropin, Vasculotropin a, Vasculotropin receptor 1, Vasculotropin receptor 2, Adenocarcinoma, Adenoma, Agar gel electrophoresis, Animal cell, Animal experiment, Animal model, Animal tissue, Antineoplastic activity, Article, Cd8+ t lymphocyte, Cecum, Cell isolation, Cell therapy, Cell viability, Centrifugation, Colon, Contamination, Controlled study, Denaturation, Dysplasia, Female, Fetal bovine serum, Fluorescence activated cell sorting, Gene expression, Goblet cell, Histology, Histopathology, Illumination, Immunotherapy, Incubation time, Lamina propria, Large intestine, Light dark cycle, Lymph follicle, Lymph node, Microphotography, Mouse, Nonhuman, Protein expression, Randomized controlled trial, Real time polymerase chain reaction, Reverse transcription, Rna extraction, Signal transduction, Spectrophotometry, Spleen cell, Staining, T cell depletion, Tumor associated leukocyte, Vegf signaling