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Sulfarotene 通过减轻 NK 细胞诱导的干性抑制结直肠癌

英文原题:Sulfarotene Inhibits Colorectal Cancer via Mitigating Natural-Killer-Cell-Induced Stemness.

查看英文原题

Sulfarotene Inhibits Colorectal Cancer via Mitigating Natural-Killer-Cell-Induced Stemness.

PubMed 2024/03/18(内容时间) Pharmaceuticals (Basel) Q1 · IF 5.7(JCR 2025)

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中文摘要

肿瘤细胞干性是驱动肿瘤复发或转移的关键因素,并显著促成结直肠癌(CRC)患者死亡。近期研究揭示,免疫活性细胞可能诱导肿瘤细胞干性,进而增强治疗耐药。本研究在有无sulfarotene处理的条件下,将CRC细胞系与自然杀伤(NK)细胞共培养,以评估肿瘤干性;并采用CRC异种移植模型,考察sulfarotene在体内逆转NK细胞活化所诱导干性的效果。结果显示,与NK细胞共培养后,CRC细胞出现显著干性特征,表现为多种癌症干细胞相关干性标志物上调;这些细胞对CRC常用化疗药奥沙利铂和伊立替康也表现出明显耐药。值得注意的是,sulfarotene在体外和体内实验中均有效逆转了改变后的干性状态。总之,sulfarotene通过抑制干性重塑,成为克服CRC对NK细胞耐受的一种有前景治疗策略。本研究强调其增强NK细胞介导免疫监视的潜力,并提出一种针对CRC的新型免疫治疗思路。

展开英文摘要原文

Tumor cell stemness stands out as a pivotal factor driving tumor recurrence or metastasis and significantly contributes to the mortality of patients with colorectal cancer (CRC). Recent research has unveiled a link between immune-active cells and the induction of tumor cell stemness, ultimately leading to heightened resistance to treatment. In this study, stemness in CRC cell lines was assessed after co-culture with natural killer (NK) cells, both with and without sulfarotene administration.

Furthermore, a CRC xenograft model was utilized to scrutinize the in vivo efficacy of sulfarotene in overcoming stemness induced by NK cell activation. As a result, CRC cells exhibited significant stemness after NK cell co-culture, as evidenced by the upregulation of several stemness markers associated with cancer stem cells.

Moreover, these cells demonstrated remarkable resistance to commonly used chemotherapy agents for CRC, such as oxaliplatin and irinotecan.

Importantly, sulfarotene effectively reversed the altered stemness of CRC cells in both in vitro and in vivo assays.

In conclusion, sulfarotene emerges as a promising therapeutic strategy for overcoming colorectal cancer resistance to NK cells by effectively inhibiting stemness remodeling.

This study underscores the potential of sulfarotene in augmenting NK-cell-mediated immune surveillance, proposing a novel immunotherapeutic approach against colorectal cancer.

论文信息

作者
Hu K、Dong Y、Zhang J、Liu M、Sun X、Cao X、Zhang P、Liu T
单位
Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.China
期刊
Pharmaceuticals (Basel, Switzerland)2024 Mar 18
原文标识
PubMed 38543173 · DOI 10.3390/ph17030387