Publication: In vitro and in vivo antineoplastic activities of solamargine in colorectal cancer through the suppression of PI3K/AKT pathway
Authors
Liu, Aihua ; Liu, Chunying
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Publisher
Universidad de Murcia. Departamento de BiologĂa Celular e HistologĂa
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DOI
https://doi.org/10.14670/HH-18-717
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info:eu-repo/semantics/article
Description
Abstract
Purpose. Previous research has demonstrated
the efficacy of SM in inhibiting tumor growth in various
cancer types. The objective of this study was to examine
the antineoplastic effects and molecular mechanisms of
Solamargine (SM) in colorectal cancer.
Methods. Colorectal cancer (CRC) cells were treated
with different concentrations of SM to evaluate the
anticancer concentration for further experimental
measurements. Additionally, the antitumor efficacy of
SM was assessed in a subcutaneously implanted tumor
model of colorectal cancer. RNA-seq and bioinformatics
analyses were employed to identify differentially
expressed genes (DEGs) and elucidate the underlying
molecular mechanisms in LoVo cells. Subsequently, the
specific mechanism of SM-mediated anti-tumor
activities was analyzed by protein expression methods.
Results. The results of in vitro assays demonstrated
that SM exhibits significant inhibitory effects on cell
proliferation, clone formation, and invasion, while also
promoting apoptosis in SW48 and LoVo cells. In a
mouse xenograft tumor model, intragastric
administration of SM at doses of 5 or 10 mg/kg
effectively suppressed tumor volume and weight, and
induced cell apoptosis in vivo. SM treatment also downregulated PCNA and Cyclin E protein expression,
contributing to the regulation of apoptosis. Further
analysis using RNA-seq, bioinformatics, and
experimental measurements revealed that SM treatment
upregulates PTEN expression, while significantly
reducing the phosphorylation levels of Akt and mTOR in
LoVo cells.
Conclusion. Our study provides further evidence to
support the notion that SM primarily induces apoptosis
in colorectal cancer cells through the inhibition of the
PI3K/Akt signaling pathway. Additionally, our
investigation demonstrated the favorable safety profile
of SM in a mouse model of colorectal cancer, thereby
suggesting its potential as a promising therapeutic
approach for the management of CRC.
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Citation
Histology and Histopathology, Vol.39, nÂş10, (2024)
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