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靶向UNC5B的齐墩果酸抑制卵巢癌细胞增殖和上皮-间质转化并增加尼拉帕利的化疗敏感性

Oleanolic Acid (OA) Targeting UNC5B Inhibits Proliferation and EMT of Ovarian Cancer Cell and Increases Chemotherapy Sensitivity of Niraparib.

作者信息

Zeng Zhen, Yu Jing, Jiang Zhongqing, Zhao Ningwei

机构信息

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China.

Department of Gynaecology, Affiliated Fuzhou First Hospital of Fujian Medical University, Fujian Medical University, Fuzhou 350009, China.

出版信息

J Oncol. 2022 Jan 6;2022:5887671. doi: 10.1155/2022/5887671. eCollection 2022.

Abstract

OBJECTIVE

To investigate the effect of OA on proliferation, migration, and epithelial-mesenchymal transition (EMT) of ovarian cancer cells by inhibiting UNC5B and to study its mechanism.

METHODS

TCGA database was used to analyze the expression of UNC5B in ovarian cancer and its relationship with prognosis. The expression of UNC5B in ovarian cancer cells was detected by qPCR assay. qRT-PCR was used to detect the changes of EMT markers after different treatments. CCK-8 assay was used to detect cell proliferation, transwell assay was used to evaluate cell migration, and clonogenesis assay was used to evaluate the effect of UNC5B on ovarian cancer cell proliferation. Meanwhile, the synergistic effect of OA on niraparib was evaluated.

RESULTS

UNC5B was highly expressed in ovarian cancer, and its expression was negatively correlated with the prognosis of ovarian cancer patients. UNC5B was highly expressed in ovarian cancer cells SKOV3 and OVCA420 compared with normal ovarian epithelial cells. In addition, silencing UNC5B inhibits the proliferation, invasion, clonogenesis, and EMT processes of ovarian cancer cells. OA inhibits proliferation, invasion, and clonogenesis of ovarian cancer cells by inhibiting UNC5B and increases the antitumor activity of niraparib.

CONCLUSION

UNC5B acts as an oncogenic gene in ovarian cancer. OA inhibits ovarian cancer cell proliferation, migration, and EMT by targeting UNC5B and increases the antitumor effect of niraparib. UNC5B is expected to be a new potential therapeutic target for ovarian cancer. OA may be used as an antitumor drug and deserves further study.

摘要

目的

通过抑制UNC5B研究油酸(OA)对卵巢癌细胞增殖、迁移及上皮-间质转化(EMT)的影响,并探讨其作用机制。

方法

利用TCGA数据库分析UNC5B在卵巢癌中的表达及其与预后的关系。采用qPCR法检测卵巢癌细胞中UNC5B的表达。运用qRT-PCR检测不同处理后EMT标志物的变化。采用CCK-8法检测细胞增殖,transwell法评估细胞迁移,克隆形成实验评估UNC5B对卵巢癌细胞增殖的影响。同时,评估OA对尼拉帕利的协同作用。

结果

UNC5B在卵巢癌中高表达,其表达与卵巢癌患者的预后呈负相关。与正常卵巢上皮细胞相比,UNC5B在卵巢癌细胞SKOV3和OVCA420中高表达。此外,沉默UNC5B可抑制卵巢癌细胞的增殖、侵袭、克隆形成及EMT过程。OA通过抑制UNC5B抑制卵巢癌细胞的增殖、侵袭和克隆形成,并增强尼拉帕利的抗肿瘤活性。

结论

UNC5B在卵巢癌中作为致癌基因发挥作用。OA通过靶向UNC5B抑制卵巢癌细胞的增殖、迁移和EMT,并增强尼拉帕利的抗肿瘤作用。UNC5B有望成为卵巢癌新的潜在治疗靶点。OA可能作为一种抗肿瘤药物,值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b593/8758276/ec841b95e4b4/JO2022-5887671.001.jpg

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