neferine/isoliensinine及其与顺铂诱导的顺铂耐药结肠癌干细胞（CSCs）凋亡的组合方案逆转顺铂耐药,Journal of Biochemical and Molecular Toxicology

当前位置： X-MOL 学术 › J. Biochem. Mol. Toxicol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

neferine/isoliensinine及其与顺铂诱导的顺铂耐药结肠癌干细胞（CSCs）凋亡的组合方案逆转顺铂耐药
Journal of Biochemical and Molecular Toxicology ( IF 3.2 ) Pub Date : 2021-12-17 , DOI: 10.1002/jbt.22967
Prasath Manogaran ₁ , Bharath Somasundaram ₁ , Vijaya Padma Viswanadha ₁

Affiliation

对结直肠癌细胞 (CRC) 的顺铂化疗伴随着剂量限制的副作用以及获得的耐药性，这意味着低治疗结果。本研究旨在评估 neferine/isoliensinine 或 neferine/isoliensinine 与顺铂联合方案对 CSCs（顺铂耐药结肠干细胞）的化学增敏作用。使用顺铂脉冲暴露于亲本 HCT-15 细胞来开发 CSC。与对照相比，Neferine/isoliensinine 或 Neferine/isoliensinine 和顺铂的组合方案对 CSC 表现出更强的细胞毒活性。集成电路₅₀发现 neferine 的剂量分别为 6.5 μM，异莲心碱的剂量为 12.5 μM，顺铂的剂量分别为 120 μM。此外，低剂量顺铂（40 μM）与 4 μM neferine/8 μM isoliensinine 的组合方案以通过等效线图描述的协同方式诱导细胞死亡。Neferine/isoliensinine 可以在 CSCs 中产生广泛的细胞内活性氧物质。Neferine/isoliensinine 或组合方案消散了线粒体膜电位并增强了细胞内 [Ca ²⁺ ] i, 是通过荧光光谱法测量的。此外，这些组合方案诱导细胞周期停滞的亚 G0 期和 PI 摄取显着增加，并减轻 CSCs 中 ERCC1 的表达。组合方案或 neferine/isolisinine 治疗通过上调 Bax、细胞色素c、caspase-3 和 PARP 切割表达同时下调 CSCs 中 BCl-2 的表达来下调细胞存活蛋白表达 (PI3K/pAkt/mTOR) 并激活线粒体介导的细胞凋亡. 我们的研究证实了 neferine/isoliensinine 或 neferine/isoliensinine 与低剂量顺铂联合方案对 CSCs 的化学增敏作用。

"点击查看英文标题和摘要"

Reversal of cisplatin resistance by neferine/isoliensinine and their combinatorial regimens with cisplatin-induced apoptosis in cisplatin-resistant colon cancer stem cells (CSCs)

Cisplatin chemotherapy to the colorectal cancer cells (CRCs) is accompanied by dose-limiting adverse effects along with the acquisition of drug resistance implicating low therapeutic outcomes. The present study is aimed to evaluate the chemosensitizing efficacy of neferine/isoliensinine or combinatorial regimen of neferine/isoliensinine with cisplatin against CSCs (cisplatin resistant colon stem cells). CSCs were developed using pulse exposure of cisplatin to parental HCT-15 cells. Neferine/isoliensinine or combinatorial regimens of Neferine/isoliensinine and cisplatin exhibited a stronger cytotoxic activity against CSCs compared to control. IC₅₀ doses were found to be 6.5 μM for neferine, 12.5 μM for isoliensinine, and 120 μM for cisplatin respectively. Furthermore, the combinatorial regimen of a low dose of cisplatin (40 μM) with 4 μM neferine/8 μM isoliensinine induced cell death in a synergistic manner as described by isobologram. Neferine/isoliensinine could confer extensive intracellular reactive oxygen species generation in CSCs. Neferine/isoliensinine or combinatorial regimens dissipated mitochondrial membrane potential and enhanced intracellular [Ca²⁺]i, which were measured by spectroflurimetry. Furthermore, these combinatorial regimens induced a significant increase in the sub G0 phase of cell cycle arrest and PI uptake and alleviated the expression of ERCC1 in CSCs. Combinatorial regimens or neferine/isoliensinine treatments downregulated the cell survival protein expression (PI3K/pAkt/mTOR) and activated mitochondria-mediated apoptosis by upregulating Bax, cytochrome c, caspase-3, and PARP cleavage expression while downregulating the BCl-2 expression in CSCs. Our study confirms the chemosensitizing efficacy of neferine/isoliensinine or combinatorial regimens of neferine/isoliensinine with a low dose of cisplatin against CSCs.

更新日期：2021-12-17

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南