Shiva Abolhasani, Armin Mahmoud Salehi Khesht, Atefeh Khodakarami, Ali Masjedi, Bentolhoda Rashidi, Sepideh Izadi, Fatemeh Karimian Noukabadi, Vahid Karpisheh, Khatereh Torabi Poudeh, Pooya Jalali, Zahra Salehi, Rafieh Bagherifar, Seyyed Sina Hejazian, AliAkbar Movassaghpour, Abbas Ali Hosseinpour Feizi, Farhad Jadidi
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引用次数: 0
Abstract
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.
期刊介绍：
Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques.
The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors.
Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.
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