Natural killer (NK) cells have exhibited promising efficacy in inhibiting cancer growth. We aimed to explorer the effect of NK cells on oxaliplatin-resistant colorectal cancer and the underlying molecular mechanism. Oxaliplatin-resistant colorectal cancer cell lines were co-cultured with NK cells to evaluate the effect on viability, proliferation, migration and invasion . Oxaliplatin-resistant colorectal cancer cells were also co-injected with NK cells into mice to establish xenograft tumor model, to assess the effect of NK cells on tumorigenesis of the oxaliplatin-resistant colorectal cancer cells. Expression of WBSCR22 gene was assessed in the oxaliplatin-resistant colorectal cancer cells following NK cell treatment to elucidate the mechanism. NK cell treatment significantly reduces growth of oxaliplatin-resistant colorectal cancer cells both and , as well as reduced WBSCR22 expression. MicroRNAs potentially targeting WBSCR22 were analyzed, and microRNA-146b-5p was found to be significantly upregulated following NK cell treatment. MicroRNA-146b-5p directly targeted WBSCR22 mRNA 3'-UTR to inhibit its expression, which was required for NK cell-induced inhibition of oxaliplatin-resistant colorectal cancer cell lines. NK cells inhibit oxaliplatin-resistant colorectal cancer by repressing WBSCR22 via upregulating microRNA-146b-5p, both of which could serve as candidates for targeted therapy against oxaliplatin-resistant colorectal cancer.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5992516 | PMC |
Publication Analysis
Top Keywords
Similar Publications
The expression of exosomal and cellular miRNAs in predicting oxaliplatin resistance in colorectal cancer cells: an in silico and in vitro study.
BMC Cancer
January 2025
Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Background: Colorectal cancer (CRC) is a common gastrointestinal cancer, and even though oxaliplatin chemotherapy is effective, there is a high likelihood of relapse, indicating the presence of oxaliplatin-resistant CRC. Therefore, it is crucial to comprehend the molecular mechanisms of oxaliplatin resistance and develop effective strategies to counter drug resistance. Numerous studies have demonstrated the close association between microRNAs (miRNAs) and drug resistance in CRC.
View Article and Find Full Text PDFOxidative Phosphorylation as a Predictive Biomarker of Oxaliplatin Response in Colorectal Cancer.
Biomolecules
October 2024
Gruop Multidisciplinar de Oncología Traslacional, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, 07122 Palma de Mallorca, Spain.
Oxaliplatin is successfully used on advanced colorectal cancer to eradicate micro-metastasis, whereas its benefits in the early stages of colorectal cancer remains controversial since approximately 30% of patients experience unexpected relapses. Herein, we evaluate the efficacy of oxidative phosphorylation as a predictive biomarker of oxaliplatin response in colorectal cancer. We found that non-responding patients exhibit low oxidative phosphorylation activity, suggesting a poor prognosis.
View Article and Find Full Text PDFMitotic Arrest Deficient 2 Like 1 Contributes to Colorectal Cancer Cell Migration, Invasion, and Oxaliplatin Resistance Through the Wnt/β-Catenin Pathway.
Chem Biol Drug Des
November 2024
Department of Gastrointestinal Surgery, Yueyang Central Hospital, Yueyang, Hunan, People's Republic of China.
Colorectal cancer (CRC) is a highly prevalent malignancy, requiring chemotherapy for advanced stages of the disease. Previously, we found that mitotic arrest deficient 2 like 1 (MAD2L1) was upregulated and facilitated malignant proliferation in CRC. However, the association between MAD2L1 expression and tumor progression, as well as chemotherapy resistance in CRC, remains unclear.
View Article and Find Full Text PDFDKK1 as a chemoresistant protein modulates oxaliplatin responses in colorectal cancer.
Oncogenesis
September 2024
National Institute of Cancer Research, National Health Research Institutes, Tainan, 704, Taiwan.
Oxaliplatin is effective against colorectal cancer (CRC), but resistance hampers treatment. We found upregulated Dickkopf-1 (DKK1, a secreted protein) in oxaliplatin-resistant (OR) CRC cell lines and DKK1 levels increased by more than 2-fold in approximately 50% of oxaliplatin-resistant CRC tumors. DKK1 activates AKT via cytoskeleton-associated protein 4 (CKAP4, a DKK1 receptor), modulating oxaliplatin responses in vitro and in vivo.
View Article and Find Full Text PDFPrediction and verification of targets for α-hederin/oxaliplatin dual-loaded rHDL modified liposomes: Reversing effector T-cells dysfunction and improving anti-COAD efficiency in vitro and in vivo.
Int J Pharm
September 2024
Department of Pharmaceutics, Shanghai Eighth People's Hospital, Jiangsu University, Shanghai 200235, China. Electronic address:
This study tried to develop the α-Hederin/Oxaliplatin (OXA) dual-loaded rHDL (α-Hederin-OXA-rHDL) modified liposomes to improve the therapeutic index on colon adenocarcinoma (COAD). The α-Hederin-OXA-rHDL were prepared and evaluated for characterizations, accumulate to tumor tissues, and antitumor activity. A thorough investigation into oxaliplatin resistant and KRAS-mutant related hub keg genes were identified and performed to assess the prognosis role of the genetic signature in COAD.
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!