Background/aim: Colorectal cancer (CRC) is one of the most common malignancies and cause of cancer-related deaths worldwide. The combination of chemotherapeutics working with different mechanisms enhances the therapeutic effects and delays the development of resistance. This study investigated the anticancer effect of the combination of ribociclib (LEE011) and irinotecan (SN38) on CRC cells.
Materials And Methods: HT-29 and SW480 cells were treated with LEE011, SN38, or the combination of LEE011 and SN38. Cell viability and cell cycle distribution were analyzed. The expression of cell cycle- and apoptosis-related proteins was determined using western blot.
Results: The combination of LEE011 and SN38 elicited a synergistic antiproliferative effect on HT-29 (PIK3CA mutation) cells, and an antagonistic antiproliferative effect on SW480 (KRAS mutation) cells. LEE011 inhibited retinoblastoma protein (Rb) phosphorylation and led to G arrest in HT-29 and SW480 cells. SN38 treatment caused a significant increase in the phosphorylation levels of Rb, cyclin B1, and CDC2 in SW480 cells and induced S phase arrest. Furthermore, SN38 treatment increased the phosphorylation levels of p53 and activated caspase-3 and caspase-8 in HT-29 and SW480 cells. LEE011-induced G arrest contributed to its synergistic antiproliferative effect with SN38 in HT-29 cells through the down-regulation of the phosphorylation of Rb. In addition, it elicited an antagonistic effect with SN38 in SW480 cells by changing the phosphorylation levels of Rb and activating caspase-8.
Conclusion: The effects of the combination of LEE011 and conventional chemotherapy drugs on CRC depend on the chemotherapy drug and the specific gene mutation harbored by tumor cells.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.21873/anticanres.16353 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Sample Preparation of Adherent Cell Lines for Flow Cytometry: Protocol Optimization-Our Experience with SW-480 colorectal cancer cell line.
Indian J Clin Biochem
January 2025
Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, Kragujevac, 34000 Serbia.
The most common method for detection of apoptosis is flow cytometry. In previously published studies there are some uncertainties and problems about the preparation of adherent cell lines for analysis. Thus, the aim of this study is to determine and describe how preparing the sample of SW-480 cells in two different ways affects the reliability of the results.
View Article and Find Full Text PDFSchiff bases targeting an Sw-480 colorectal cell line: synthesis, characterization, ds-DNA binding and anticancer studies.
RSC Adv
January 2025
Centre for Genetics and Inherited Diseases (CGID), Taibah University Madinah Saudi Arabia.
In present studies, six Schiff bases were prepared, characterized and evaluated for their anti-tumor activity against the colorectal cancer cell line SW-480. The test compounds were characterized by various physico-chemical techniques such as M. P.
View Article and Find Full Text PDFTRPV4 as a Novel Regulator of Ferroptosis in Colon Adenocarcinoma: Implications for Prognosis and Therapeutic Targeting.
Dig Dis Sci
January 2025
Ningxia Medical University, Xing Qing Block, Shengli Street No.1160, Yin Chuan City, 750004, Ningxia Province, People's Republic of China.
Background: Colon adenocarcinoma (COAD) is a leading cause of cancer-related mortality worldwide. Transient receptor potential vanilloid 4 (TRPV4), a calcium-permeable non-selective cation channel, has been implicated in various cancers, including COAD. This study investigates the role of TRPV4 in colon adenocarcinoma and elucidates its potential mechanism via the ferroptosis pathway.
View Article and Find Full Text PDFAnti-colorectal cancer actions of Glycyrrhiza uralensis Fisch. and its underlying mechanism via HPLC integration and network pharmacological approaches.
Phytomedicine
January 2025
College of Pharmacy, Xinjiang Medical University, Urumqi, 830000, China; School of Biological and Food Engineering, Engineering Research Center for Development and High Value Utilization of Genuine Medicinal Materials in North Anhui Province, Suzhou University, Suzhou, Anhui, 234000, China; Department of Analytical Chemistry and Food Science, Faculty of Food Science and Technology, University of Vigo-Ourense Campus, Ourense E-32004, Spain. Electronic address:
Background: The therapeutic and prognostic outcomes for colorectal cancer (CRC) remain unsatisfactory. Among multiple reported bioactive functionalities of Glycyrrhiza uralensis Fisch. one vital recently reported activity is its therapeutic role against numerous cancers but limited information is available related to its underlying key mechanisms and therapeutically active ingredients, especially against CRC treatment.
View Article and Find Full Text PDFMechanism Analysis of the Effect of Cordycepin on Colorectal Cancer via Network Pharmacology and Experiment.
Comb Chem High Throughput Screen
January 2025
Shanghai Key Laboratory of Molecular Imaging, Jiading District Central Hospital Affiliated Shanghai University of Medicine and Health Sciences, Shanghai 201318, China.
Objective: Colorectal Cancer (CRC) has attracted much attention due to its high mortality and morbidity. Cordycepin, also known as 3'-deoxyadenosine (3'-dA), exhibits many biological functions, including antibacterial, anti-inflammatory, antiviral, anti-tumor, and immunomodulatory effects. It has been proven to show anticancer activity in both laboratory research studies and living organisms.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!