细胞氨酸脱氨酶-TRAIL表达人体脂肪干细胞抑制瘤生长的割抵抗性前列腺癌携带小鼠具有较少的毒性
Jae Heon Kim1, Hyun Young Lee1, In Seok Hong2
1Department of Urology, Soonchunhyang University Seoul Hospital, Soonchunhyang University Medical College, Seoul 04401, Republic of Korea.
International journal of molecular sciences
|February 13, 2026
概括
工程干细胞表达自杀基因和TRAIL有效地向并减少抵抗割的前列腺癌生长. 这种综合疗法在治疗晚期前列腺癌方面表现出有前途,毒性最小.
科学领域:
- 在瘤学瘤学.
- 干细胞疗法是一种干细胞疗法.
- 基因治疗 基因治疗
背景情况:
- 抗割前列腺癌 (CRPC) 仍然是一个重大的临床挑战.
- 与瘤亡因子相关的诱导亡的配体 (TRAIL) 选择性地诱导癌细胞亡.
- 人类脂肪衍生干细胞 (ADSCs) 具有瘤定位能力.
研究的目的:
- 为了评估ADSCs的疗效,该ADSCs被设计为表达细胞氨酸脱氨酶 (CD) 和可溶性TRAIL (sTRAIL),用于CRPC治疗.
- 在临床前模型中评估工程ADSC和5-细胞素 (5-FC) 的联合治疗效果.
主要方法:
- 通过使用lentiviral向量,工程化永生的人类ADSCs (hTERT-ADSC) 来表达CD和sTRAIL (ADSC.CD.sTRAIL).
- 通过RT-PCR评估化学吸引剂配体/受体表达.
- 在试验室中评估了5-FC治疗的细胞毒性和亡诱导.
- 使用皮下CRPC小鼠模型进行了体内研究.
主要成果:
- 改造的ADSCs表现出对前列腺癌细胞的增强迁移.
- 在体外,5-FC治疗显著降低了癌细胞活力,增加了细胞灭亡.
- 在体内研究显示,与对照小鼠相比,治疗小鼠的瘤体积显著减少.
- 没有观察到与治疗相关的显著毒性.
结论:
- 使用CD和sTRAIL设计的ADSCs与5-FC相结合,代表了抑制CRPC瘤生长的有力策略.
- 这种向基因细胞治疗方法显示了CRPC的显著治疗潜力.
- 组合疗法耐受性良好,表明其临床适用性.
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