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表达羧基酯酶-TRAIL 的人脂肪干细胞抑制去势抵抗性前列腺癌荷瘤小鼠肿瘤生长且毒性较小。

Carboxyl Esterase-TRAIL Expressing Human Adipose Stem Cells Inhibit Tumor Growth in Castration-Resistant Prostate Cancer-Bearing Mice with Less Toxicity.

机构信息

Department of Urology, Soonchunhyang University Seoul Hospital, Soonchunhyang University Medical College, Seoul, Korea.

Department of Pharmacology, 37977Ajou University School of Medicine, Suwon, Republic of Korea.

出版信息

Technol Cancer Res Treat. 2022 Jan-Dec;21:15330338221093146. doi: 10.1177/15330338221093146.

DOI:10.1177/15330338221093146
PMID:35491733
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9069602/
Abstract

It has been proposed that CRPC treatment with reduced systemic toxicity can be achieved by employing genes that express enzymes that activate pharmacological agents. In this paper, we report our study that used human adipose-derived stem cells (ADSC), rabbit CE, and human TRAIL with reduced toxicity to explore how tumor development can be suppressed in CRPC-bearing mouse models. and directional migration of ADSC.CE.sTRAIL cells toward PC3 cells was significantly stimulated.ADSC.CE.sTRAIL showed higher suicide effects than did ADSC, ADSC.CE, or ADSC.sTRAIL under CPT-11 treatment. PC3 cells co-cultured with ADSC.CE.TRAIL showed higher cytotoxicity than did CPT-11 monotherapy, ADSC.CE, or ADSC.sTRAIL under CPT-11 treatment. ADSC.CE.sTRAIL showed higher apoptosis than did CPT-11 monotherapy, ADSC.CE, or ADSC.sTRAIL under CPT-11 treatment. In the study, ADSC.CE.sTRAIL inhibited tumor growth more than did CPT-11 monotherapy, ADSC.CE, or ADSC.sTRAIL under CPT-11 treatment. The evidence suggests that patients' own ADSC could be used in clinical trials for CRPC treatment based on therapeutic stem cells that express CE and TRAIL complex genes.

摘要

有人提出,通过使用表达能激活药物的酶的基因,可以实现降低毒性的 CRPC 治疗。在本文中,我们报告了一项研究,该研究使用了人脂肪来源的干细胞(ADSC)、兔 CE 和 TRAIL,降低了毒性,以探索如何在患有 CRPC 的小鼠模型中抑制肿瘤发展。ADSC.CE.sTRAIL 细胞对 PC3 细胞的定向迁移显著受到刺激。与 CPT-11 治疗相比,ADSC.CE.sTRAIL 显示出更高的自杀效应,而 ADSC、ADSC.CE 或 ADSC.sTRAIL 则没有。与 CPT-11 单药治疗、ADSC.CE 或 ADSC.sTRAIL 相比,共培养的 PC3 细胞显示出更高的细胞毒性。与 CPT-11 单药治疗、ADSC.CE 或 ADSC.sTRAIL 相比,ADSC.CE.sTRAIL 显示出更高的细胞凋亡。在这项研究中,ADSC.CE.sTRAIL 抑制肿瘤生长的效果优于 CPT-11 单药治疗、ADSC.CE 或 ADSC.sTRAIL。有证据表明,基于表达 CE 和 TRAIL 复合物基因的治疗性干细胞,患者自身的 ADSC 可用于 CRPC 治疗的临床试验。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8db1/9069602/1531956e9eed/10.1177_15330338221093146-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8db1/9069602/9b9893346052/10.1177_15330338221093146-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8db1/9069602/edb4c7f0a1df/10.1177_15330338221093146-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8db1/9069602/684476475e17/10.1177_15330338221093146-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8db1/9069602/e03d2bdc2412/10.1177_15330338221093146-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8db1/9069602/28d31bb91a75/10.1177_15330338221093146-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8db1/9069602/1531956e9eed/10.1177_15330338221093146-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8db1/9069602/9b9893346052/10.1177_15330338221093146-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8db1/9069602/edb4c7f0a1df/10.1177_15330338221093146-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8db1/9069602/684476475e17/10.1177_15330338221093146-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8db1/9069602/e03d2bdc2412/10.1177_15330338221093146-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8db1/9069602/28d31bb91a75/10.1177_15330338221093146-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8db1/9069602/1531956e9eed/10.1177_15330338221093146-fig6.jpg

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The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research.ARRIVE 指南 2.0:报告动物研究的更新指南。
Br J Pharmacol. 2020 Aug;177(16):3617-3624. doi: 10.1111/bph.15193. Epub 2020 Jul 14.
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