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埃里安宁通过调控 Wnt/β-连环蛋白通路并激活 caspase-3 诱导细胞凋亡,从而在体外和体内抑制顺铂耐药肺腺癌细胞的进展。

Erianin inhibits the progression of DDP-resistant lung adenocarcinoma by regulating the Wnt/β-catenin pathway and activating the caspase-3 for apoptosis in vitro and in vivo.

机构信息

Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.

Department of General practice, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.

出版信息

Hereditas. 2024 Nov 27;161(1):48. doi: 10.1186/s41065-024-00351-x.

DOI:10.1186/s41065-024-00351-x
PMID:39605083
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11600767/
Abstract

BACKGROUND

Platinum-based chemotherapy is one of the main treatments for lung adenocarcinoma (LUAD). However, the toxic side effects and drug resistance of chemotherapeutic drugs on normal cells are still a thorny problem in clinical treatment. Dendrobium is one of the three largest genera of Orchidaceous family, which has ornamental and medicinal value. Dendrobium is mainly distributed in the tropics and subtropics of South Asia, Oceania and other regions, with 1547 species of Dendrobium currently known. In China, "Shi hu" and "Tie pi shi hu" are well-known traditional medicines and have been included in the Chinese Pharmacopoeia (Editorial Board of Chinese Pharmacopoeia, 2020). Erianin is a natural product isolated from Dendrobium and is considered as a potential anticancer molecule due to its remarkable anti-tumor effects through various mechanisms, among which induced cancer cell apoptosis, inhibited invasion and migration. This study preliminarily explored the mechanism of Erianin inhibiting the progression of cisplatin (DDP) resistant LUAD in vivo and in vitro.

METHODS

The effect of Erianin on the proliferation of DDP-resistant LUAD cells was detected by CCK-8 assay, wound healing assay and cloning assay. Transwell assay was used to evaluate the effect of Erianin on cell invasion and migration. The changes of cell cycle and apoptosis were detected by flow cytometry and TUNEL assay. Finally, the effects of Erianin on cell function and signaling pathway-related protein expression in vivo and in vitro were examined based on the enrichment analysis.

RESULTS

Erianin could inhibit the proliferation, invasion and migration, induce apoptosis, altered cell cycle of DDP-resistant LUAD cells, and reverse the resistance to DDP. Western blotting results showed that Erianin exerted its anti-tumor effects by regulating the Wnt/β-catenin cascade in DDP-resistant LUAD cells.

CONCLUSION

Erianin may exerted its anti-tumor effect in DDP-resistant LUAD cells by regulating the Wnt3/β-Catenin/Survivin/Bcl-2/Caspase-3/Cyclin D1 axis.

摘要

背景

铂类化疗是肺腺癌(LUAD)的主要治疗方法之一。然而,化疗药物对正常细胞的毒副作用和耐药性仍然是临床治疗中的一个难题。石斛是兰科三大属之一,具有观赏和药用价值。石斛主要分布在南亚、大洋洲等热带和亚热带地区,目前已知有 1547 种石斛。在中国,“石斛”和“铁皮石斛”是著名的传统药材,已被列入《中国药典》(中国药典编辑委员会,2020 年)。蛇菰宁是从石斛中分离得到的天然产物,由于其通过多种机制发挥显著的抗肿瘤作用,被认为是一种有潜力的抗癌分子,其中包括诱导癌细胞凋亡、抑制侵袭和迁移。本研究初步探讨了蛇菰宁在体内和体外抑制顺铂(DDP)耐药 LUAD 进展的机制。

方法

用 CCK-8 法、划痕愈合实验和克隆形成实验检测蛇菰宁对 DDP 耐药 LUAD 细胞增殖的影响。Transwell 实验用于评估蛇菰宁对细胞侵袭和迁移的影响。通过流式细胞术和 TUNEL 实验检测细胞周期和凋亡的变化。最后,基于富集分析,检测蛇菰宁在体内和体外对细胞功能和信号通路相关蛋白表达的影响。

结果

蛇菰宁能抑制 DDP 耐药 LUAD 细胞的增殖、侵袭和迁移,诱导细胞凋亡,改变细胞周期,逆转 DDP 耐药性。Western blot 结果表明,蛇菰宁通过调节 DDP 耐药 LUAD 细胞中的 Wnt/β-catenin 级联发挥其抗肿瘤作用。

结论

蛇菰宁可能通过调节 Wnt3/β-Catenin/Survivin/Bcl-2/Caspase-3/Cyclin D1 轴在 DDP 耐药 LUAD 细胞中发挥其抗肿瘤作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/612d/11600767/478e5ff3a306/41065_2024_351_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/612d/11600767/9d85e83691a5/41065_2024_351_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/612d/11600767/fcf86eb2a29a/41065_2024_351_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/612d/11600767/33dbe5e10cb2/41065_2024_351_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/612d/11600767/478e5ff3a306/41065_2024_351_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/612d/11600767/9d85e83691a5/41065_2024_351_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/612d/11600767/fcf86eb2a29a/41065_2024_351_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/612d/11600767/33dbe5e10cb2/41065_2024_351_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/612d/11600767/478e5ff3a306/41065_2024_351_Fig4_HTML.jpg

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