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氧代白藜芦醇通过抑制蛋白激酶 B(AKT)的激活增强顺铂对上皮性卵巢癌细胞的抗癌作用。

Oxyresveratrol Enhances the Anti-Cancer Effect of Cisplatin against Epithelial Ovarian Cancer Cells through Suppressing the Activation of Protein Kinase B (AKT).

机构信息

Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.

Graduate School, Chiang Mai University, Chiang Mai 50200, Thailand.

出版信息

Biomolecules. 2024 Sep 9;14(9):1140. doi: 10.3390/biom14091140.


DOI:10.3390/biom14091140
PMID:39334906
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11430010/
Abstract

Epithelial ovarian carcinoma poses a significant challenge due to its resistance to chemotherapy and propensity for metastasis, thereby reducing the effectiveness of conventional treatments. Hence, the identification of novel compounds capable of augmenting the anti-cancer efficacy of platinum-based chemotherapy is imperative. Oxyresveratrol (OXY), a derivative of resveratrol, has been demonstrated to possess antiproliferative and apoptosis-inducing effects across various cancer cell lines. Notably, OXY appears to exert its effects by inhibiting the PI3K/AKT/mTOR signaling pathway. However, the synergistic potential of OXY in combination with cisplatin against epithelial ovarian cancer has not yet been elucidated. The current study investigated the synergistic effects of OXY and cisplatin on the ovarian cancer cell lines SKOV3 and TOV21G. We found that OXY significantly enhanced cisplatin's ability to reduce cell viability, induce apoptosis, induce cell cycle arrest, and increase the proportion of cells in the sub-G1 phase. Furthermore, OXY treatment alone dose-dependently inhibited the production of anti-apoptotic proteins including Mcl-1, Bcl-xL, and XIAP under EGF activation. Mechanistically, OXY suppressed the PI3K/AKT/mTOR signaling pathway by reducing phosphorylated AKT, while having no discernible effect on the MAPK pathway. These findings highlight OXY's potential to enhance ovarian cancer cell sensitivity to chemotherapy, suggesting its development as a pharmaceutical adjunct for clinical use in combination therapies.

摘要

上皮性卵巢癌由于对化疗的耐药性和转移倾向,使其成为治疗的一大挑战,从而降低了传统治疗的效果。因此,寻找能够增强基于铂类化疗的抗癌疗效的新型化合物是至关重要的。白藜芦醇(OXY)是白藜芦醇的衍生物,已被证明在各种癌细胞系中具有抗增殖和诱导凋亡的作用。值得注意的是,OXY 似乎通过抑制 PI3K/AKT/mTOR 信号通路发挥作用。然而,OXY 与顺铂联合治疗上皮性卵巢癌的协同作用尚未阐明。本研究探讨了 OXY 和顺铂对卵巢癌细胞系 SKOV3 和 TOV21G 的协同作用。我们发现,OXY 显著增强了顺铂降低细胞活力、诱导凋亡、诱导细胞周期停滞和增加亚 G1 期细胞比例的能力。此外,OXY 单独处理在 EGF 激活下,呈剂量依赖性地抑制抗凋亡蛋白包括 Mcl-1、Bcl-xL 和 XIAP 的产生。在机制上,OXY 通过降低磷酸化 AKT 来抑制 PI3K/AKT/mTOR 信号通路,而对 MAPK 通路没有明显影响。这些发现强调了 OXY 增强卵巢癌细胞对化疗敏感性的潜力,提示其作为一种药物联合物,可用于联合治疗的临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a19/11430010/dde8faab18b9/biomolecules-14-01140-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a19/11430010/1a519655f3c7/biomolecules-14-01140-g001a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a19/11430010/77fbbb1bd6e9/biomolecules-14-01140-g002a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a19/11430010/a65de19bbd9c/biomolecules-14-01140-g003a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a19/11430010/d9c438642ea0/biomolecules-14-01140-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a19/11430010/9ad19dd3de47/biomolecules-14-01140-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a19/11430010/765e21bfa206/biomolecules-14-01140-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a19/11430010/e499311de0a2/biomolecules-14-01140-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a19/11430010/dde8faab18b9/biomolecules-14-01140-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a19/11430010/1a519655f3c7/biomolecules-14-01140-g001a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a19/11430010/77fbbb1bd6e9/biomolecules-14-01140-g002a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a19/11430010/a65de19bbd9c/biomolecules-14-01140-g003a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a19/11430010/d9c438642ea0/biomolecules-14-01140-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a19/11430010/9ad19dd3de47/biomolecules-14-01140-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a19/11430010/765e21bfa206/biomolecules-14-01140-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a19/11430010/e499311de0a2/biomolecules-14-01140-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a19/11430010/dde8faab18b9/biomolecules-14-01140-g008.jpg

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[2]
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[3]
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[5]
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引用本文的文献

[1]
Urtica dioica leaf infusion enhances cisplatin-induced apoptosis in ovarian cancer cells in vitro.

BMC Complement Med Ther. 2025-8-13

[2]
Metal-based molecules in the treatment of cancer: From bench to bedside.

Oncol Res. 2025-3-19

本文引用的文献

[1]
Oxyresveratrol in Breast Cancer Cells: Synergistic Effect with Chemotherapeutics Doxorubicin or Melphalan on Proliferation, Cell Cycle Arrest, and Cell Death.

Pharmaceutics. 2024-6-29

[2]
Comparative Studies of Resveratrol, Oxyresveratrol and Dihydrooxyresveratrol on Doxorubicin-Treated Lung Cancer Cells.

Asian Pac J Cancer Prev. 2024-3-1

[3]
Inhibitory actions of oxyresveratrol on the PI3K/AKT signaling cascade in cervical cancer cells.

Biomed Pharmacother. 2024-1

[4]
Cisplatin in Ovarian Cancer Treatment-Known Limitations in Therapy Force New Solutions.

Int J Mol Sci. 2023-4-20

[5]
The function of natural compounds in important anticancer mechanisms.

Front Oncol. 2023-1-4

[6]
Role of RAS signaling in ovarian cancer.

F1000Res. 2022

[7]
Worldwide Burden, Risk Factors, and Temporal Trends of Ovarian Cancer: A Global Study.

Cancers (Basel). 2022-4-29

[8]
Effect of resveratrol and oxyresveratrol on deferoxamine-induced cancer stem cell marker expression in human head and neck squamous cell carcinoma.

J Oral Biol Craniofac Res. 2022

[9]
Oxyresveratrol Inhibits TNF-α-Stimulated Cell Proliferation in Human Immortalized Keratinocytes (HaCaT) by Suppressing AKT Activation.

Pharmaceutics. 2021-12-28

[10]
Targeting PI3K/Akt signal transduction for cancer therapy.

Signal Transduct Target Ther. 2021-12-16

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