1. Vactosertib potently improves anti-tumor properties of 5-FU for colon cancer.
- Author
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Binabaj, Maryam Moradi, Asgharzadeh, Fereshteh, Rahmani, Farzad, Al-Asady, Abdulridha Mohammed, Hashemzehi, Milad, Soleimani, Atena, Avan, Amir, Mehraban, Saeedeh, Ghorbani, Elnaz, Ryzhikov, Mikhail, Khazaei, Majid, and Hassanian, Seyed Mahdi
- Subjects
COMBINATION drug therapy ,FLOW cytometry ,IN vitro studies ,ANTI-inflammatory agents ,PROTEIN kinases ,RESEARCH funding ,ANTINEOPLASTIC agents ,POLYMERASE chain reaction ,ENZYME-linked immunosorbent assay ,CELL proliferation ,APOPTOSIS ,TREATMENT effectiveness ,IN vivo studies ,CANCER patients ,COLON tumors ,CELL lines ,CANCER chemotherapy ,MICE ,GENE expression ,ANIMAL experimentation ,MEMBRANE glycoproteins ,MATRIX metalloproteinases ,FLUOROURACIL ,STAINS & staining (Microscopy) ,TRANSFORMING growth factors-beta ,CELL receptors ,DISEASE progression ,PHARMACODYNAMICS ,CHEMICAL inhibitors - Abstract
Background Several studies have shown that the TGF-β signaling pathway plays a critical role in colorectal cancer (CRC) pathogenesis. The aim of the current study is to investigate the therapeutic potential of Vactosertib (EW-7197), a selective inhibitor of TGF-β receptor type I, either alone or in combination with the standard first-line chemotherapeutic treatment, 5-Fluorouracil (5-FU), in CRC progression in both cellular and animal models. Methods Real-Time PCR, Zymography, enzyme-linked immunosorbent assay (ELISA), Hematoxylin and Eosin (H&E) tissue staining, and Flow cytometry techniques were applied to determine the anti-tumor properties of this novel TGF-β inhibitor in in vitro (CT-26 cell line) and in vivo (inbred BALB/C mice) samples. Results Our findings showed that Vactosertib decreased cell proliferation and induced spheroid shrinkage. Moreover, this inhibitor suppressed the cell cycle and its administration either alone or in combination with 5-FU induced apoptosis by regulating the expression of p53 and BAX proteins. It also improved 5-FU anti-cancer effects by decreasing the tumor volume and weight, increasing tumor necrosis, and regulating tumor fibrosis and inflammation in an animal model. Vactosertib also enhanced the inhibitory effect of 5-FU on invasive behavior of CRC cells by upregulating the expression of E-cadherin and inhibiting MMP-9 enzymatic activity. Conclusion This study demonstrating the potent anti-tumor effects of Vactosertib against CRC progression. Our results clearly suggest that this inhibitor could be a promising agent reducing CRC tumor progression when administered either alone or in combination with standard treatment in CRC patients. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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