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Vactosertib potently improves anti-tumor properties of 5-FU for colon cancer.
- Source :
- DARU: Journal of Pharmaceutical Sciences; Dec2023, Vol. 31 Issue 2, p109-203, 11p
- Publication Year :
- 2023
-
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]
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 15608115
- Volume :
- 31
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- DARU: Journal of Pharmaceutical Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 176823386
- Full Text :
- https://doi.org/10.1007/s40199-023-00474-y