Purpose: Colorectal cancer (CRC) is one of the most prevalence malignancies in a different society with a high rate of death. The KRAS and p38α axes have critical roles in the development, migration, and growth of numerous tumors, such as colorectal malignancy. KRAS mutation acts as an oncogene in various cancers and is correlated with the poor prognosis in colorectal tumors. Also, p38α plays different roles and exhibits tissue-dependent activity. In some tissues act as an oncogene while in others act as a tumor suppressor. In this research, we try to understand the effect of the P38α and KRAS genes suppression by specific siRNAs on the SW480 cell line progression.
Methods: We evaluate the impact of the P38α and KRAS gene knockdown by special siRNA on the growth and development of the SW480 cell line. SW480 cell line was treated with KRAS and P38α siRNAs, and the cell viability, gene expression, migration ability, and rate of apoptosis were evaluated with MTT assay, real-time PCR, scratch test, and flow cytometry.
Results: After treatment of the cancer cell with KRAs and P38α siRNAs, cell viability reduced to 29.16%. Also, the expression levels of the KRAS and P38α genes reduced to 26.34% and 16.06%, respectively. Apoptosis rate after combination therapy with KRAS and P38α siRNAs increased to 72.1. Also, we found that these siRNAs suppress cell migration in SW480 cell lines.
Conclusion: The current study showed that combination therapy with p38α and KRAS siRNA may be considered a novel therapy for colorectal tumor in future.
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http://dx.doi.org/10.1007/s12029-021-00667-1 | DOI Listing |
Int J Biol Sci
January 2025
Department of Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.
Most tumors initially respond to treatment, yet refractory clones subsequently develop owing to resistance mechanisms associated with cancer cell plasticity and heterogeneity. We used a chemical biology approach to identify protein targets in cancer cells exhibiting diverse driver mutations and representing models of tumor lineage plasticity and therapy resistance. An unbiased screen of a drug library was performed against cancer cells followed by synthesis of chemical analogs of the most effective drug.
View Article and Find Full Text PDFMed J Islam Repub Iran
September 2024
Department of Oncology, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan.
Background: The narrative review aims to explore CRC pathogenesis by deciphering genetic-environmental interactions, analyzing the tumor microenvironment's role, and assessing treatment responses. These objectives seek to enhance clinical decision-making and improve CRC patient care through a comprehensive understanding of the disease.
Methods: A narrative review from 2019 to 2024 on colorectal cancer (CRC) pathogenesis and treatment strategies was conducted.
J Chem Inf Model
January 2025
Computer-Aided Drug Discovery, Global Discovery Chemistry, Novartis Biomedical Research, 181 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
Targeted covalent inhibition is a powerful therapeutic modality in the drug discoverer's toolbox. Recent advances in covalent drug discovery, in particular, targeting cysteines, have led to significant breakthroughs for traditionally challenging targets such as mutant KRAS, which is implicated in diverse human cancers. However, identifying cysteines for targeted covalent inhibition is a difficult task, as experimental and in silico tools have shown limited accuracy.
View Article and Find Full Text PDFExp Mol Med
January 2025
Department of Molecular Science and Technology, Ajou University, Suwon, South Korea.
Most cancer mutation profiling studies are laboratory-based and lack direct clinical application. For clinical use, it is necessary to focus on key genes and integrate them with relevant clinical variables. We aimed to evaluate the prognostic value of the dosage of the KRAS G12 mutation, a key pancreatic ductal adenocarcinoma (PDAC) variant and to investigate the biological mechanism of the prognosis associated with the dosage of the KRAS G12 mutation.
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