Browsing by Subject "PI3K/Akt"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Publication
    Open Access
    In vitro and in vivo antineoplastic activities of solamargine in colorectal cancer through the suppression of PI3K/AKT pathway
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2024) Liu, Aihua; Liu, Chunying
    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.
  • Thumbnail Image
    Publication
    Open Access
    Roles of long-non-coding RNAs in cancer therapy through the PI3K/Akt signalling pathway
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Ting-Wei Lee, Katherine; Gopalan, Vinod; King-yin Lam, Alfred
    The vital need for Akt in maintaining basic cellular function has highlighted its importance in carcinogenesis. Unfortunately, Akt inhibitor development outcome has remained poor, as most of them have failed to show significant clinical benefit to cancer patients during the clinical trials. Recently, a new class of non-coding RNAs, known as long non-coding RNAs (lncRNAs), which show high tissue specificity, have demonstrated great influence in cancer progression and/or cancer inhibition. As both Akt signalling pathways and lncRNAs play such innate roles in carcinogenesis, identifying the specific roles that these lncRNAs play within this pathway may represent a novel research avenue for developing Akt inhibitors with better therapeutic properties. In addition, understanding the diverse mechanism by which lncRNAs regulate gene expression can assist in deciphering the fundamentals of carcinogenesis. The focus of interest should be on the lncRNAs, which affect Akt and finding the link between lncRNAs and Akt pathways associated with carcinogenesis. LncRNAs within the Akt pathways could affect multiple pathways in a particular cancer type, which ultimately creates an intricate web of connections between the pathways. In summary, lncRNAs have tremendous potential in cancer diagnosis, assessing cancer patient prognosis and in developing new therapeutic options for patients with resistance to current cancer therapies. Thus, understanding how lncRNAs influence the Akt pathway is essential for the development of novel and effective cancer therapies.