PMID- 28912871 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220408 IS - 1792-0981 (Print) IS - 1792-1015 (Electronic) IS - 1792-0981 (Linking) VI - 14 IP - 4 DP - 2017 Oct TI - Paeonol enhances the sensitivity of human ovarian cancer cells to radiotherapy-induced apoptosis due to downregulation of the phosphatidylinositol-3-kinase/Akt/phosphatase and tensin homolog pathway and inhibition of vascular endothelial growth factor. PG - 3213-3220 LID - 10.3892/etm.2017.4877 [doi] AB - Radiotherapy is a vital and effective method to treat solid tumors. However, in many tumor types, development of resistance of cancer cells and cytotoxicity in normal tissues presents a major therapeutic problem. It is therefore crucial to identify and develop novel sensitizing agents that may improve the response to radiation therapy without causing any adverse effects. The present study aimed to investigate whether paeonol, a bioactive flavonoid, was able to confer sensitivity to radiation in human ovarian cancer cells. The human ovarian cancer cell lines SKOV-3 and OVCAR-3 were exposed to varying doses of radiation (2, 4 or 6 Gy) in the presence or absence of paeonol (25, 50 or 100 microM). Radiosensitivity was assessed by measuring cell viability using a CCK-8 assay and Annexin V/PI staining. Expression of vascular endothelial growth factor (VEGF), hypoxia inducible factor-1alpha (HIF-1alpha), proteins of the phosphatidylinositol-3-kinase (PI3K)/Akt pathway and apoptotic pathway proteins [caspase-3, Bcl-2-associated death promoter, B-cell lymphoma (Bcl)-2, Bcl-2-associated X and Bcl-extra large (Bcl-xL)] were also assessed. Paeonol treatment enhanced apoptosis of SKOV-3 and OVCAR-3 cells that were exposed to radiation. The expression of Bcl-2 and Bcl-xL were markedly upregulated in these cells. Treatment with paeonol concentrations of 50 and 100 microM caused a significant downregulation of VEGF, HIF-1alpha and PI3K/Akt pathway proteins. Paeonol effectively enhanced the sensitivity of ovarian cancer cells to radiation by significantly altering regulation of the proteins of the PI3K/Akt pathway, in addition to downregulating VEGF and HIF-1alpha. FAU - Zhou, Hai-Mei AU - Zhou HM AD - Department of Obstetrics and Gynecology, The Affiliated Hospital of Shandong Medical College, Linyi, Shandong 276401, P.R. China. FAU - Sun, Qin-Xiang AU - Sun QX AD - Department of Internal Medicine, The Affiliated Hospital of Shandong Medical College, Linyi, Shandong 276401, P.R. China. FAU - Cheng, Yan AU - Cheng Y AD - Department of Obstetrics and Gynecology, Obstetrics and Gynecology Hospital Affiliated To Fudan University, Shanghai 200090, P.R. China. LA - eng PT - Journal Article DEP - 20170803 PL - Greece TA - Exp Ther Med JT - Experimental and therapeutic medicine JID - 101531947 PMC - PMC5585758 OTO - NOTNLM OT - apoptosis OT - ovarian cancer OT - paeonol OT - phosphatidylinositol-3-kinase/Akt pathway OT - radiotherapy OT - vascular endothelial growth factor EDAT- 2017/09/16 06:00 MHDA- 2017/09/16 06:01 PMCR- 2017/08/03 CRDT- 2017/09/16 06:00 PHST- 2015/11/17 00:00 [received] PHST- 2016/11/18 00:00 [accepted] PHST- 2017/09/16 06:00 [entrez] PHST- 2017/09/16 06:00 [pubmed] PHST- 2017/09/16 06:01 [medline] PHST- 2017/08/03 00:00 [pmc-release] AID - ETM-0-0-4877 [pii] AID - 10.3892/etm.2017.4877 [doi] PST - ppublish SO - Exp Ther Med. 2017 Oct;14(4):3213-3220. doi: 10.3892/etm.2017.4877. Epub 2017 Aug 3.