The Mechanism of Active Components of Traditional Chinese Medicine in Treating Ovarian Cancer by PI3K/Akt Signaling

doi:10.12280/gjszjk.20250247

Abstract

Abstract:

Ovarian cancer (OC) is one of the common malignant tumors in women. Most of patients are diagnosed at the advanced stage due to its insidious onset, resulting in poor clinical treatment outcomes. Currently, the treatment of OC mainly relies on chemotherapy and surgery, but the chemotherapy resistance and adverse reactions remain the clinical challenge. Studies have shown that the abnormal expressions of multiple signaling pathways are related to the pathogenesis of OC, such as the abnormal activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. The active components of traditional Chinese medicine can regulate the PI3K/Akt signaling pathway to inhibit the proliferation, invasion, migration and angiogenesis of OC cells, to promote the apoptosis of OC cells, and to improve the chemosensitivity of OC cells. This review summarizes the role of the PI3K/Akt signaling pathway in OC and the research progress on the mechanism of the active components of traditional Chinese medicine in regulating the PI3K/Akt signaling pathway, with the aim of providing a reference for the clinical application of traditional Chinese medicine in the treatment or adjutant therapy of OC.

Key words: Ovarian neoplasms, Antineoplastic agents (TCD), Phosphatidylinositol 3-kinases, Proto-oncogene proteins c-akt, Cell proliferation, Cell movement, Apoptosis

ZHANG Li-qian, LU Run-guo, WANG Yu, SHI Bai-chao, WU Xiao-ke. The Mechanism of Active Components of Traditional Chinese Medicine in Treating Ovarian Cancer by PI3K/Akt Signaling[J]. Journal of International Reproductive Health/Family Planning, 2025, 44(5): 434-440.

References 40

[1]	Stewart C, Ralyea C, Lockwood S. Ovarian Cancer: An Integrated Review[J]. Semin Oncol Nurs, 2019, 35(2):151-156. doi: 10.1016/j.soncn.2019.02.001. pmid: 30867104
[2]	Hu X, Lv J, Qin C, et al. Global and China burden of hormone-related cancers and risk factors, 1990-2021: results from the Global Burden of Disease Study 2021[J]. BMC Public Health,2025, 25(1):1566. doi: 10.1186/s12889-025-22768-3.
[3]	Zhang R, Zhang Z, Xie L, et al. In vitro analysis of the molecular mechanisms of ursolic acid against ovarian cancer[J]. BMC Complement Med Ther, 2025, 25(1):65. doi: 10.1186/s12906-025-04808-y. pmid: 39984915
[4]	Xu M, Li X, Yuan C, et al. Ursolic Acid Inhibits Glycolysis of Ovarian Cancer via KLF5/PI3K/AKT Signaling Pathway[J]. Am J Chin Med, 2024, 52(7):2211-2231. doi: 10.1142/S0192415X2450085X.
[5]	Glaviano A, Foo A, Lam HY, et al. PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer[J]. Mol Cancer, 2023, 22(1):138. doi: 10.1186/s12943-023-01827-6. pmid: 37596643
[6]	Panwar V, Singh A, Bhatt M, et al. Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease[J]. Signal Transduct Target Ther, 2023, 8(1):375. doi: 10.1038/s41392-023-01608-z.
[7]	Bergholz JS, Wang Q, Wang Q, et al. PI3Kβ controls immune evasion in PTEN-deficient breast tumours[J]. Nature, 2023, 617(7959):139-146. doi: 10.1038/s41586-023-05940-w.
[8]	冯叶雯, 安庆文, 杨楚琪, 等. 基于PTEN/PI3K/AKT信号通路探讨隐丹参酮抑制结直肠癌的作用机制[J]. 中华中医药杂志, 2024, 39(12):6666-6670.
[9]	弓翠屏, 王英. 洛伐他汀调控转化生长因子-β诱导的卵巢癌细胞增殖、侵袭和迁移的机制研究[J]. 安徽医药, 2023, 27(1):69-73. doi: 10.3969/j.issn.1009-6469.2023.01.015.
[10]	Yang HW, Lan Y, Li A, et al. Myricetin suppresses TGF-β-induced epithelial-to-mesenchymal transition in ovarian cancer[J]. Front Pharmacol, 2023,14:1288883. doi: 10.3389/fphar.2023.1288883.
[11]	Magouliotis DE, Minervini F, Cioffi U, et al. The Role of Epithelial-Mesenchymal Transition in Malignant Pleural Mesothelioma: From Pathogenesis to Diagnosis and Treatment[J]. Cells, 2025, 14(8):585. doi: 10.3390/cells14080585.
[12]	Yuan C, Zhu C, Lv Q, et al. Discovery of Arene Ruthenium(II) Complexes as Potential VEGF Inhibitors for Glioblastoma Metastasis Suppression[J]. J Med Chem, 2024, 67(21):18724-18740. doi:10.1021/acs.jmedchem.4c00797.
[13]	马孝秋, 左韬, 马贤德, 等. 基于VEGFA/VEGFR2-PI3K/AKT信号轴探讨化瘀明目方含药血清抑制高糖及VEGF诱导人视网膜微血管内皮细胞血管新生的分子机制[J]. 中药新药与临床药理, 2025, 36(2):197-205. doi: 10.19378/j.issn.1003-9783.2025.02.005.
[14]	Lee D, Kim R, Son SR, et al. Inhibitory effect of ginsenglactone A from Panax ginseng on the tube formation of human umbilical vein endothelial cells and migration of human ovarian cancer cells[J]. J Ginseng Res, 2023, 47(2):246-254. doi: 10.1016/j.jgr.2022.08.003.
[15]	Dou L, Yan Y, Lu E, et al. Composition analysis and mechanism of Guizhi Fuling capsule in anti-cisplatin-resistant ovarian cancer[J]. Transl Oncol, 2025,52:102244. doi: 10.1016/j.tranon.2024.102244.
[16]	宋玉芳, 张前, 刘英杰, 等. miR-425-5p调节PTEN/PI3K/AKT轴对卵巢癌细胞顺铂敏感性的影响[J]. 中国细胞生物学学报, 2023, 45(8):1182-1192. doi: 10.11844/cjcb.2023.08.0005.
[17]	Chen J, Ji Z, Wu D, et al. MYBL2 promotes cell proliferation and inhibits cell apoptosis via PI3K/AKT and BCL2/BAX/Cleaved-caspase-3 signaling pathway in gastric cancer cells[J]. Sci Rep, 2025, 15(1):9148. doi: 10.1038/s41598-025-93022-4.
[18]	Liu D, Li L, Zhang J, et al. Berberine promotes apoptosis and inhibits the migration of oral squamous carcinoma cells through inhibition of the RAGE/PI3K/AKT/mTOR pathway[J]. Biomed Pharmacother, 2025,187:118147. doi: 10.1016/j.biopha.2025.118147.
[19]	Li Z, Liu M, Li J, et al. Diosmetin alleviates AFB1-induced endoplasmic reticulum stress, autophagy, and apoptosis via PI3K/AKT pathway in mice[J]. Ecotoxicol Environ Saf, 2025,292:117997. doi: 10.1016/j.ecoenv.2025.117997.
[20]	Zheng Y, Li X, Huang G, et al. Shuang Bailian mixture enhanced the anti-cancer effect of cisplatin by regulating PI3K-Akt-Bcl 2 signaling pathway[J]. J Ethnopharmacol, 2025,343:119462. doi: 10.1016/j.jep.2025.119462.
[21]	Zhu J, Lin S, Zou X, et al. Mechanisms of autophagy and endoplasmic reticulum stress in the reversal of platinum resistance of epithelial ovarian cancer cells by naringin[J]. Mol Biol Rep, 2023, 50(8):6457-6468. doi: 10.1007/s11033-023-08558-3. pmid: 37326754
[22]	Lin C, Zeng Z, Lin Y, et al. Naringenin suppresses epithelial ovarian cancer by inhibiting proliferation and modulating gut microbiota[J]. Phytomedicine, 2022,106:154401. doi: 10.1016/j.phymed.2022.154401.
[23]	Gao J, Fu Y, Song L, et al. Proapoptotic Effect of Icariin on Human Ovarian Cancer Cells via the NF-κB/PI3K-AKT Signaling Pathway: A Network Pharmacology-Directed Experimental Investigation[J]. Am J Chin Med, 2022, 50(2):589-619. doi: 10.1142/S0192415X22500239.
[24]	Wang S, Gao J, Li Q, et al. Study on the regulatory mechanism and experimental verification of icariin for the treatment of ovarian cancer based on network pharmacology[J]. J Ethnopharmacol, 2020,262:113189. doi: 10.1016/j.jep.2020.113189.
[25]	Dhanaraj T, Mohan M, Arunakaran J. Quercetin attenuates metastatic ability of human metastatic ovarian cancer cells via modulating multiple signaling molecules involved in cell survival, proliferation, migration and adhesion[J]. Arch Biochem Biophys, 2021,701:108795. doi: 10.1016/j.abb.2021.108795.
[26]	Hasan A, Kalinina EV, Tatarskiy VV, et al. Suppression of the Antioxidant System and PI3K/Akt/mTOR Signaling Pathway in Cisplatin-Resistant Cancer Cells by Quercetin[J]. Bull Exp Biol Med, 2022, 173(6):760-764. doi: 10.1007/s10517-022-05626-9.
[27]	何静, 严如根, 金国钰, 等. 冬凌草甲素体内外抗卵巢癌活性及相关机制研究[J]. 郑州大学学报(医学版), 2023, 58(4):480-489. doi: 10.13705/j.issn.1671-6825.2023.03.023.
[28]	Yang Q, Fei Z, Huang C. Betulin terpenoid targets OVCAR-3 human ovarian carcinoma cells by inducing mitochondrial mediated apoptosis, G2/M phase cell cycle arrest, inhibition of cell migration and invasion and modulating mTOR/PI3K/AKT signalling pathway[J]. Cell Mol Biol(Noisy-le-grand), 2021, 67(2):14-19. doi: 10.14715/cmb/2021.67.2.3.
[29]	余瑛, 张群贵, 崔华子, 等. 姜黄素联合顺铂调控PI3K/Akt信号通路对卵巢癌耐药细胞增殖、迁移和凋亡的影响[J]. 中国免疫学杂志, 2023, 39(7):1415-1419. doi: 10.3969/j.issn.1000-484X.2023.07.013.
[30]	Sandhiutami N, Arozal W, Louisa M, et al. Curcumin Nanoparticle Enhances the Anticancer Effect of Cisplatin by Inhibiting PI3K/AKT and JAK/STAT3 Pathway in Rat Ovarian Carcinoma Induced by DMBA[J]. Front Pharmacol, 2020,11:603235. doi: 10.3389/fphar.2020.603235.
[31]	Alharbi HM, Alqahtani T, Alamri AH, et al. Nanotechnological synergy of mangiferin and curcumin in modulating PI3K/Akt/mTOR pathway: a novel front in ovarian cancer precision therapeutics[J]. Front Pharmacol, 2023,14:1276209. doi: 10.3389/fphar.2023.1276209.
[32]	Hankittichai P, Thaklaewphan P, Wikan N, et al. Resveratrol Enhances Cytotoxic Effects of Cisplatin by Inducing Cell Cycle Arrest and Apoptosis in Ovarian Adenocarcinoma SKOV-3 Cells through Activating the p38 MAPK and Suppressing AKT[J]. Pharmaceuticals(Basel), 2023, 16(5):755. doi: 10.3390/ph16050755.
[33]	Meng R, Zhang Z. Gallic Acid Inhibits the Proliferation and Migration of Ovarian Cancer Cells via Inhibition of the PI3K-AKT Pathway and Promoting M1-Like Macrophage Polarization[J]. Anal Cell Pathol(Amst), 2025,2025:3880719. doi: 10.1155/ancp/3880719.
[34]	吕思慧, 梁金兰, 邓明晶, 等. 白鲜碱靶向调控PI3K/KEAP1信号抑制卵巢癌细胞增殖并诱导自噬及凋亡[J]. 中国癌症防治杂志, 2023, 15(3):285-291. doi: 10.3969/j.issn.1674-5671.2023.03.06.
[35]	申屠乐, 陈梦静, 李影影, 等. 粉防己碱通过抑制PI3K/AKT/mTOR信号通路诱导卵巢癌细胞自噬[J]. 中国病理生理杂志, 2020, 36(8):1428-1433. doi: 10.3969/j.issn.1000-4718.2020.08.012.
[36]	舒美玲, 吴悦, 叶映泉, 等. 华蟾素调控PI3K/AKT通路逆转卵巢癌A2780/DDP细胞顺铂耐药的作用机制[J]. 安徽医科大学学报, 2024, 59(4):671-677,741. doi: 10.19405/j.cnki.issn1000-1492.2024.04.018.
[37]	Wang Y, Li Y, Wang L, et al. Cinnamaldehyde Suppressed EGF-Induced EMT Process and Inhibits Ovarian Cancer Progression Through PI3K/AKT Pathway[J]. Front Pharmacol, 2022,13:779608. doi: 10.3389/fphar.2022.779608.
[38]	史璟, 郭勇峰, 常江. 蛇床子素调节PI3K/AKT/MAPK信号通路对卵巢癌细胞增殖、凋亡、迁移和侵袭的影响[J]. 中国优生与遗传杂志, 2022, 30(7):1115-1119.
[39]	Wang X, Xu X, Jiang G, et al. Dihydrotanshinone I inhibits ovarian cancer cell proliferation and migration by transcriptional repression of PIK3CA gene[J]. J Cell Mol Med, 2020, 24(19):11177-11187. doi: 10.1111/jcmm.15660.
[40]	Yu G, Nanding A. Salidroside overcomes cisplatin resistance in ovarian cancer via the inhibition of CRNDE-mediated autophagy[J]. Mol Cell Biochem, 2025, 480(5):3097-3116. doi: 10.1007/s11010-024-05168-w.