Timosaponin AIII Inhibits Migration and Invasion Abilities in Colorectal Cancer Through Inactivation of PI3K-AKT-mTOR Pathway

Title:Timosaponin AIII Inhibits Migration and Invasion Abilities in Colorectal Cancer Through Inactivation of PI3K-AKT-mTOR Pathway

Volume: 26

Author(s): Hao-Ran Xu, Long-Xun Zhu, Jin-Di Liu, Xiang-Fan Chen, Nan Sheng, Qing Fang and Pan-Feng Feng*

Affiliation:

• Department of pharmacy, Affiliated hospital 2 of Nantong University, Nantong, China
• Nantong Key Laboratory of Innovative Research on Rheumatology and Immunology, Nantong, China

Keywords: Colorectal cancer, Timosaponin AIII, metastases, epithelial–mesenchymal transition, PI3K-AKT-mTOR pathway.

Abstract:

Introduction: Metastases frequently occur in patients with colorectal cancer, resulting in a higher death rate. The study aimed to evaluate the mechanism by which Ti-mosaponin AIII affects colorectal cancer metastases.

Methods: Different concentrations of Timosaponin AIII were used to treat colorectal cancer cell lines. The CCK8 assay was used to evaluate how Timosaponin AIII affected cell viability. Transwell chamber assays were employed to evaluate the impact of the treatment on the migratory and invasive abilities of colorectal cancer cells. The influence of Timosaponin AIII on apoptosis was detected through flow cytometry, and western blot, PCR, and immunofluorescence staining were utilized to assess its effect on the expression of proteins. The effect of Timosaponin AIII on tumor growth was studied by using xenograft tumor models.

Results: In this study, we observed that, in comparison with the control group, Timosaponin AIII could inhibit the proliferation, migration, and invasive capabilities of colorectal cancer cell lines and promote the process of apoptosis. Timosaponin AIII is capable of enhancing the phosphorylation levels of PI3K, AKT, and mTOR, as well as increasing E - E-cadherin while decreasing N - N-cadherin, Vimentin, Snail, and Slug, thereby inhibiting the epithelial-mesenchymal transition process.

Discussion: The present study has limitations, as the mechanistic investigations were mainly conducted at the cellular level. Future studies should validate the molecular mechanisms through animal models.

Conclusions: Timosaponin AIII restrains the activation of the PI3K-AKT-mTOR signal pathway, thereby regulating the EMT process to suppress metastases of colorectal cancer cell lines. This research provides a critical foundation for the clinical application of Ti-mosaponin AIII in colorectal cancer treatment.

Cite this article as:

Xu Hao-Ran, Zhu Long-Xun, Liu Jin-Di, Chen Xiang-Fan, Sheng Nan, Fang Qing and Feng Pan-Feng*, Timosaponin AIII Inhibits Migration and Invasion Abilities in Colorectal Cancer Through Inactivation of PI3K-AKT-mTOR Pathway, Current Cancer Drug Targets 2026; 26 () . https://dx.doi.org/10.2174/0115680096383861251003074135