Vactosertib potently improves anti-tumor properties of 5-FU for colon cancer.
In: DARU: Journal of Pharmaceutical Sciences, Jg. 31 (2023-12-01), Heft 2, S. 109-119
Online
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Zugriff:
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]
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Vactosertib potently improves anti-tumor properties of 5-FU for colon cancer.
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Autor/in / Beteiligte Person: | 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 ; Hassanian, Seyed Mahdi |
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Zeitschrift: | DARU: Journal of Pharmaceutical Sciences, Jg. 31 (2023-12-01), Heft 2, S. 109-119 |
Veröffentlichung: | 2023 |
Medientyp: | academicJournal |
ISSN: | 1560-8115 (print) |
DOI: | 10.1007/s40199-023-00474-y |
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