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胆石酸诱导人肾母细胞瘤细胞凋亡:一种非选择性的治疗选择。

Lithocholic bile acid induces apoptosis in human nephroblastoma cells: a non-selective treatment option.

机构信息

Department of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.

Department of Pediatric Nephrology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.

出版信息

Sci Rep. 2020 Nov 23;10(1):20349. doi: 10.1038/s41598-020-77436-w.

Abstract

Lithocholic bile acid (LCA) has been reported to selectively kill cancer cells within many tumor cell lines including neuroblastoma or glioblastoma. Wilms' tumor shares similarities with neuro- and glioblastoma. Hence, the aim of the study was to evaluate the effects of LCA on nephroblastoma. To test the effects of LCA, nephroblastoma cell line WT CLS1 was used. SK NEP1 was tested as well. It was originally classified as a nephroblastoma cell line but was meanwhile reclassified as an ewing sarcoma cell line. As control cell lines HEK 293 from embryonic kidney and RC 124 from adult kidney tissue as well as podocytes were used. The effects were evaluated using proliferation assay, caspase activity assay, FACS and Western blot. LCA showed a dose and time-dependent selective effect inducing apoptosis in nephroblastoma cells. However, these effects were not limited to the nephroblastoma cell line but also affected control kidney cell lines and the sarcoma cells; only podocytes are significantly less affected by LCA (at dosages < 200 µm). There were no significant differences regarding the TGR5 receptor expression. The study showed that LCA has a strong, yet unselective effect on all used in vitro cell-lines, sparing the highly differentiated podocytes in lower concentrations. Further studies are needed to verify our results before dismissing LCA as an anti-cancer drug.

摘要

胆酸(LCA)已被报道选择性地杀死许多肿瘤细胞系中的癌细胞,包括神经母细胞瘤或神经胶质瘤。Wilms 瘤与神经母细胞瘤和神经胶质瘤具有相似之处。因此,本研究的目的是评估 LCA 对肾母细胞瘤的影响。为了测试 LCA 的作用,使用了肾母细胞瘤细胞系 WT CLS1。同时还测试了 SK NEP1。它最初被归类为肾母细胞瘤细胞系,但同时被重新归类为尤文肉瘤细胞系。作为对照细胞系,使用了来自胚胎肾的 HEK 293 和来自成人肾组织的 RC 124 以及足细胞。通过增殖测定、半胱天冬酶活性测定、FACS 和 Western blot 来评估作用。LCA 显示出剂量和时间依赖性的选择性作用,诱导肾母细胞瘤细胞凋亡。然而,这些作用不仅限于肾母细胞瘤细胞系,还影响对照肾细胞系和肉瘤细胞;只有足细胞受 LCA 的影响明显较小(在剂量 < 200µm 时)。TGR5 受体表达没有显著差异。该研究表明,LCA 对所有使用的体外细胞系都有强烈但非选择性的作用,在较低浓度下可保护高度分化的足细胞。在排除 LCA 作为抗癌药物之前,需要进一步的研究来验证我们的结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a578/7683553/5f7d743a24c6/41598_2020_77436_Fig1_HTML.jpg

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