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氧化锌纳米颗粒通过激活内质网应激和促进自噬来抑制卵巢癌细胞的恶性进展和化疗耐药性。

Zinc oxide nanoparticles inhibit malignant progression and chemotherapy resistance of ovarian cancer cells by activating endoplasmic reticulum stress and promoting autophagy.

作者信息

Gu Wenli, Yang Caihong

机构信息

Department of Gynecology, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750001, P.R. China.

出版信息

Exp Ther Med. 2023 Sep 14;26(5):508. doi: 10.3892/etm.2023.12207. eCollection 2023 Nov.

DOI:10.3892/etm.2023.12207
PMID:37840563
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10570763/
Abstract

The mortality rate of ovarian cancer (OC) is high, posing a serious threat to women's lives. Zinc oxide nanoparticles (ZnO-NPs) show great potential in the treatment of cancer. However, the mechanism of ZnO-NPs in inhibiting the malignant proliferation and chemotherapy resistance of OC has remained elusive. In the present study, ZnO-NPs at different concentrations were used to treat SKOV3 cells, and subsequently, analyses including the Cell Counting Kit-8 assay, EDU staining, colony-formation assay, flow cytometry, wound-healing assay, Transwell assay and western blot were used to detect cell proliferation, invasion, migration, epithelial-mesenchymal transition (EMT) and chemotherapy resistance, as well as endoplasmic reticulum stress (ERS)- and autophagy-related indicators. Finally, the mechanisms of action of ZnO-NPs on OC were examined by adding ERS inhibitor 4-phenylbutyric acid (4-PBA) and autophagy inhibitor 3-methyladenine (3-MA). It was found that ZnO-NPs inhibited SKOV3 cell proliferation, facilitated apoptosis and induced cell cycle arrest. Furthermore, ZnO-NPs inhibited the invasion, migration and EMT of SKOV3 cells. ZnO-NPs also inhibited chemotherapy resistance of SKOV3 cells. ZnO-NPs activated ERS and promoted autophagy. The addition of 4-PBA or 3-MA significantly reversed the effects of ZnO-NPs on SKOV3 cells. Overall, ZnO-NPs inhibit the malignant progression and the chemotherapy resistance of SKOV3 cells by activating ERS and promoting autophagy.

摘要

卵巢癌（OC）的死亡率很高，对女性生命构成严重威胁。氧化锌纳米颗粒（ZnO-NPs）在癌症治疗中显示出巨大潜力。然而，ZnO-NPs抑制OC恶性增殖和化疗耐药性的机制仍不清楚。在本研究中，使用不同浓度的ZnO-NPs处理SKOV3细胞，随后，采用包括细胞计数试剂盒-8检测、EDU染色、集落形成检测、流式细胞术、伤口愈合检测、Transwell检测和蛋白质免疫印迹法等分析方法，检测细胞增殖、侵袭、迁移、上皮-间质转化（EMT）和化疗耐药性，以及内质网应激（ERS）和自噬相关指标。最后，通过添加ERS抑制剂4-苯基丁酸（4-PBA）和自噬抑制剂3-甲基腺嘌呤（3-MA），研究ZnO-NPs对OC的作用机制。结果发现，ZnO-NPs抑制SKOV3细胞增殖，促进细胞凋亡并诱导细胞周期阻滞。此外，ZnO-NPs抑制SKOV3细胞的侵袭、迁移和EMT。ZnO-NPs还抑制SKOV3细胞的化疗耐药性。ZnO-NPs激活ERS并促进自噬。添加4-PBA或3-MA可显著逆转ZnO-NPs对SKOV3细胞的影响。总体而言，ZnO-NPs通过激活ERS和促进自噬来抑制SKOV3细胞的恶性进展和化疗耐药性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdcf/10570763/23c7db91ccb6/etm-26-05-12207-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdcf/10570763/940d9c28e8cc/etm-26-05-12207-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdcf/10570763/8e8ab1011115/etm-26-05-12207-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdcf/10570763/2480d3ecaac2/etm-26-05-12207-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdcf/10570763/6a217487ab68/etm-26-05-12207-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdcf/10570763/f6b0223c8a57/etm-26-05-12207-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdcf/10570763/51bde9effc7e/etm-26-05-12207-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdcf/10570763/23c7db91ccb6/etm-26-05-12207-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdcf/10570763/940d9c28e8cc/etm-26-05-12207-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdcf/10570763/8e8ab1011115/etm-26-05-12207-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdcf/10570763/2480d3ecaac2/etm-26-05-12207-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdcf/10570763/6a217487ab68/etm-26-05-12207-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdcf/10570763/f6b0223c8a57/etm-26-05-12207-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdcf/10570763/51bde9effc7e/etm-26-05-12207-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdcf/10570763/23c7db91ccb6/etm-26-05-12207-g06.jpg

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