吉西他滨和氟比洛芬增强间充质干细胞介导的对癌细胞系的细胞毒性作用。

Gemcitabine and Flurbiprofen Enhance Cytotoxic Effects on Cancer Cell Lines Mediated by Mesenchymal Stem Cells.

作者信息

Kawulok Agata, Borzdziłowska Paulina, Głowala-Kosińska Magdalena, Fidyk Wojciech, Smagur Andrzej, Łasut-Szyszka Barbara, Gdowicz-Kłosok Agnieszka, Mitrus Iwona, Wilkiewicz Marcin, Chwieduk Agata, Burdalska Daria, Korfanty Joanna, Giebel Sebastian, Rojkiewicz Marcin, Bak Andrzej, Kozik Violetta

机构信息

Institute of Chemistry, University of Silesia, Szkolna 9, 40-007 Katowice, Poland.

Department of Bone Marrow Transplantation and Oncohematology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Wybrzeze Armii Krajowej 15, 44-101 Gliwice, Poland.

出版信息

Int J Mol Sci. 2025 Jun 27;26(13):6212. doi: 10.3390/ijms26136212.

DOI:10.3390/ijms26136212

PMID:40649990

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12250333/

Abstract

Mesenchymal stem cells (MSCs) have recently shown great promise as potential anticancer drug delivery carriers. MSCs exhibit tropism to inflammatory sites, such as tumor beds, and resistance to chemotherapeutics. The aim of this study was to examine the efficacy of gemcitabine (GEM) conjugated with flurbiprofen (FLU) as a potential agent enhancing the GEM cytotoxic effect. Pancreatic cancer cell lines (PCCs), including PANC-1, AsPC-1, and BxPC-3, were studied meticulously. Moreover, the usefulness of bone-marrow-derived mesenchymal stem cells (BM-MSCs) treated with GEM and FLU, and the conditioned media from above these cells (CM) as elements supporting the in vitro action of GEM, inducing apoptosis, necrosis, and inhibiting the cell cycle, was tested. The results showed that CM-GEM exhibited higher cytotoxicity towards the selected PCCs compared to GEM alone. Furthermore, the obtained data revealed lower sensitivity of these cells to treatment, which promotes the utilization of BM-MSCs as potential drug carriers. Based on the presented findings, it seems that applying FLU in the antiproliferative effect of GEM might be regarded as an effective strategy in the therapy of pancreatic cancer, especially in the inhibition of proliferation and induction of cancer cell death.

摘要

间充质干细胞（MSCs）最近作为潜在的抗癌药物递送载体展现出了巨大的前景。MSCs表现出对炎症部位（如肿瘤床）的趋向性以及对化疗药物的抗性。本研究的目的是检验吉西他滨（GEM）与氟比洛芬（FLU）偶联作为增强GEM细胞毒性作用的潜在药物的疗效。对包括PANC-1、AsPC-1和BxPC-3在内的胰腺癌细胞系（PCCs）进行了细致研究。此外，还测试了用GEM和FLU处理的骨髓间充质干细胞（BM-MSCs）以及这些细胞的条件培养基（CM）作为支持GEM体外作用、诱导凋亡、坏死和抑制细胞周期的因素的有效性。结果表明，与单独使用GEM相比，CM-GEM对所选PCCs表现出更高的细胞毒性。此外，获得的数据显示这些细胞对治疗的敏感性较低，这促进了将BM-MSCs用作潜在的药物载体。基于所呈现的研究结果，在GEM的抗增殖作用中应用FLU似乎可被视为治疗胰腺癌的一种有效策略，尤其是在抑制增殖和诱导癌细胞死亡方面。