Статья

Advancing the therapeutic effectiveness of paclitaxel in chronic lymphocytic leukemia through the simultaneous inhibition of NOTCH1 and SF3B1

Shiva AbolhasaniImmunology Research Center, Tabriz University of Medical Sciences, Tabriz, IranArmin Mahmoud Salehi KheshtImmunology Research Center, Tabriz University of Medical Sciences, Tabriz, IranAtefeh KhodakaramiStudent Research Committee, Tabriz University of Medical Sciences, Tabriz, IranAli MasjediCenter for Translational Cancer Research (TranslaTUM), School of Medicine, Technical University of Munich, 81675, Munich, GermanyBentolhoda RashidiImmunology Research Center, Tabriz University of Medical Sciences, Tabriz, IranSepideh IzadiResearch Center for Integrative Medicine in Aging, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, IranFatemeh Karimian NoukabadiImmunology Research Center, Tabriz University of Medical Sciences, Tabriz, IranVahid KarpishehImmunology Research Center, Tabriz University of Medical Sciences, Tabriz, IranKhatereh Torabi PoudehImmunology Research Center, Tabriz University of Medical Sciences, Tabriz, IranPooya JalaliBasic and Molecular Epidemiology of Gastrointestinal Disorders Research Centre, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, IranZahra SalehiHematology, Oncology and Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, IranRafieh BagherifarStudent Research Committee, Tabriz University of Medical Sciences, Tabriz, IranSeyyed Sina HejazianImmunology Research Center, Tabriz University of Medical Sciences, Tabriz, IranAli Akbar MovassaghpourHematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, IranAbbas Ali Hosseinpour FeiziDepartment of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, IranFarhad Jadidi‐NiaraghDepartment of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. [email protected]

2025en

ABI

Аннотация

BACKGROUND: Chemoresistance is still a significant obstacle to cancer therapy. Overexpression of the splicing factor 3b subunit 1 (SF3B1) and neurogenic locus notch homolog protein 1 (NOTCH1) factors is typically found in chronic lymphocytic leukemia (CLL), leading to the development of chemotherapy resistance. OBJECTIVE: The current investigation aims to evaluate the chemosensitivity of CLL cells by blocking NOTCH1 and SF3B1 using chitosan lactate (CL) nanoparticles (NPs). METHODS: We used CL-NPs loaded with anti-NOTCH1 and -SF3B1 small interfering RNAs (siRNAs) in combination with paclitaxel (PTX) to suppress NOTCH1 and SF3B1 in peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BMMCs) isolated from CLL cases to assess the impact of this therapeutic strategy on leukemic cell chemosensitivity. Further, the competing endogenous RNA (ceRNA) network that regulates NOTCH1 and -SF3B1 was constructed and enriched. RESULTS: Our findings showed that CL-NPs loaded with anti-NOTCH1/-SF3B1 siRNAs-PTX significantly suppressed NOTCH1 and SF3B1 expression in PBMCs and BMMCs isolated from CLL cases in comparison with the untreated samples, leading to increased leukemic cell sensitivity to PTX and decreased the proliferative capacity of leukemic cells. The enrichment analysis highlighted the fundamental pathways where the NOTCH1- and SF3B1-associated ceRNA network exerts its influence in the context of CLL. CONCLUSIONS: This study implies the efficacy of combined therapy by CL-NPs loaded with anti-NOTCH1/-SF3B1 siRNAs and PTX as a novel therapeutic strategy for CLL, even though further studies are required to warrant the findings.

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Идентификаторы

DOI: 10.1186/s12935-025-03702-4

Цитирования и источники

Цитирований: 3Использованных источников: 0

Показатели — AkademScholar