Association of KRAS, NRAS, BRAF and PIK3CA gene mutations with clinicopathological features, prognosis and ring finger protein 215 expression in patients with colorectal cancer

Wu, Jing-Bo; Li, Xiao-Jing; Liu, Hui; Liu, Yong-Juan; Liu, Xiu-Ping

doi:10.3892/br.2023.1686

Cited by 3 publications

(1 citation statement)

References 63 publications

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“…In addition, resistance to chemotherapy and targeted therapy is still a major challenge to improve the survival rate and prognosis of CRC patients [ 8 , 9 , 10 ]. Genetic mutations among CRC patients, such as APC, BRAF, EGFR, KRAS and PIK3CA, could influence the response to specific therapies, such as anti-EGFR and immunotherapy [ 11 , 12 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Anti-Cancer Mechanisms of Diarylpentanoid MS17 (1,5-Bis(2-hydroxyphenyl)-1,4-pentadiene-3-one) in Human Colon Cancer Cells: A Proteomics Approach

Hon,

Zainal Abidin,

Abas

et al. 2024

IJMS

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Diarylpentanoids are synthesized to overcome curcumin’s poor bioavailability and low stability to show enhanced anti-cancer effects. Little is known about the anti-cancer effects of diarylpentanoid MS17 (1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one) in colon cancer cells. This study aimed to elucidate molecular mechanisms and pathways modulated by MS17 in colon cancer based on proteomic profiling of primary SW480 and metastatic SW620 colon cancer cells. Cytotoxicity and apoptotic effects of MS17 were investigated using MTT assay, morphological studies, and Simple Western analysis. Proteomic profiling using LC/MS analysis identified differentially expressed proteins (DEPs) in MS17-treated cells, with further analysis in protein classification, gene ontology enrichment, protein–protein interaction network and Reactome pathway analysis. MS17 had lower EC50 values (SW480: 4.10 µM; SW620: 2.50 µM) than curcumin (SW480: 17.50 µM; SW620: 13.10 µM) with a greater anti-proliferative effect. MS17 treatment of 1× EC50 induced apoptotic changes in the morphology of SW480 and SW620 cells upon 24 h treatment. A total of 24 and 92 DEPs (fold change ≥ 1.50) were identified in SW480 and SW620 cells, respectively, upon MS17 treatment of 2× EC50 for 24 h. Pathway analysis showed that MS17 may induce its anti-cancer effects in both cells via selected DEPs associated with the top enriched molecular pathways. RPL and RPS ribosomal proteins, heat shock proteins (HSPs) and ubiquitin–protein ligases (UBB and UBC) were significantly associated with cellular responses to stress in SW480 and SW620 cells. Our findings suggest that MS17 may facilitate the anti-proliferative and apoptotic activities in primary (SW480) and metastatic (SW620) human colon cancer cells via the cellular responses to stress pathway. Further investigation is essential to determine the alternative apoptotic mechanisms of MS17 that are independent of caspase-3 activity and Bcl-2 protein expression in these cells. MS17 could be a potential anti-cancer agent in primary and metastatic colon cancer cells.

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Section: Introductionmentioning

confidence: 99%

Anti-Cancer Mechanisms of Diarylpentanoid MS17 (1,5-Bis(2-hydroxyphenyl)-1,4-pentadiene-3-one) in Human Colon Cancer Cells: A Proteomics Approach

Hon,

Zainal Abidin,

Abas

et al. 2024

IJMS

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New Perspectives in Colorectal Cancers Treatment, the Role of MicroRNAs

Belova,

Spirina,

Avgustinovich

et al. 2024

CDT

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The main epidemiological and clinical data on colorectal cancer, as well as the features of molecular pathology, are discussed in the literature review. Efforts are being putto identify promising targets, particularly small non-coding nucleotide sequences, which can lead to new treatments for this disease. The discovery of significant mutations that contribute to the development of colorectal tumors is a major step in the advancement of molecular oncology, as these mutations give rise to heterogeneous tumors that differ in their origin. These mutations play a significant role in the progression of the disease and are now being targeted for treatment. The prognosis for a disease is influenced by the patient's sensitivity to antitumor therapy. However, new approaches to finding effective targets for antitumor treatments face new fundamental challenges due to clinical issues. These issues include the epigenetic regulation of markers of oncogenesis, which allows for the development of new therapeutic strategies. RNA interference, in particular, has been linked to non-copying RNA sequences such as microRNAs. These microRNAs are associated with certain processes that can influence all aspects of oncogenesis. The diversity of microRNAs allows for a differentiated approach when treating tumors in various locations.

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Synergistic Effects of the Combination of Alpelisib (PI3K Inhibitor) and Ribociclib (CDK4/6 Inhibitor) in Preclinical Colorectal Cancer Models

Aslam,

Richards,

Fay

et al. 2024

IJMS

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The CDK4/6 inhibitor Ribociclib has shown limited efficacy as a monotherapy in colorectal cancer (CRC). However, combining Ribociclib with targeted therapies could present a viable strategy for treating CRC. This study evaluated the combination of Ribociclib and the PI3K inhibitor Alpelisib across four distinct cell lines representing different mutational statuses (PIK3CA/KRAS wild-type, KRAS-mutated, PIK3CA-mutated, and PIK3CA/KRAS-mutated). We analyzed the drugs’ impact on key proteins involved in the PI3K pathway, cell cycle regulation, and apoptosis. The combination of Alpelisib and Ribociclib demonstrated a synergistic anti-proliferative effect across all cell lines, leading to a simultaneous decrease in pRB, pAKT, and p-S6 levels, and a more comprehensive suppression of the PI3K/AKT/mTOR pathway. Additionally, there was an upregulation of the apoptotic marker, p-BCL2, in cells treated with the combination compared to controls. In vivo studies using Caco-2, LS1034, and SNUC4 xenografts revealed a significant reduction in tumour growth with the combination therapy compared to single-agent treatments. These findings suggest that combining Alpelisib and Ribociclib could be a promising therapeutic approach for CRC, warranting further clinical exploration.

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Association of KRAS, NRAS, BRAF and PIK3CA gene mutations with clinicopathological features, prognosis and ring finger protein 215 expression in patients with colorectal cancer

Cited by 3 publications

References 63 publications

Anti-Cancer Mechanisms of Diarylpentanoid MS17 (1,5-Bis(2-hydroxyphenyl)-1,4-pentadiene-3-one) in Human Colon Cancer Cells: A Proteomics Approach

Anti-Cancer Mechanisms of Diarylpentanoid MS17 (1,5-Bis(2-hydroxyphenyl)-1,4-pentadiene-3-one) in Human Colon Cancer Cells: A Proteomics Approach

New Perspectives in Colorectal Cancers Treatment, the Role of MicroRNAs

Synergistic Effects of the Combination of Alpelisib (PI3K Inhibitor) and Ribociclib (CDK4/6 Inhibitor) in Preclinical Colorectal Cancer Models

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