Resveratrol suppresses the growth and metastatic potential of cervical cancer by inhibiting STAT3Tyr705 phosphorylation

Cancer Medicine - Tập 9 Số 22 - Trang 8685-8700 - 2020
Xiaodong Sun1, Qianqian Xu1, Lian Zeng1, Lixia Xie1, Qiang Zhao1, Hongxia Xu1, Xuanbin Wang1, Nan Jiang2, Pan Fu1, Ming Sang1
1Hubei Institute of Parkinson’s Disease at Xiangyang No.1 People’s Hospital, Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, People’s Republic of China
2Hubei Province Hospital of Traditional Chinese Medicine Hubei Province Academy of Traditional Chinese Medicine Wuhan People’s Republic of China

Tóm tắt

AbstractAberrant signal transducer and activator of transcription 3 (STAT3) signaling promotes the initiation and progression of cancer in humans by either inhibiting apoptosis or inducing cell proliferation, angiogenesis, invasion, and metastasis. The role of resveratrol（RES）in inhibiting the STAT3 signaling pathway in vivo, particularly in cervical cancer is still unknown. This study aims to investigate the role of STAT3 and its phosphorylation in RES‐mediated suppression of cervical cancer. The effects of RES on cervical cancer were determined by examining tumor tissues, their histological changes, and the volume and weight of tumor tissues grown from HeLa cells injected in female athymic BALB/C nude mice. The structure and target interaction of RES were virtually screened using the molecular docking program Autodock Vina. The status of phosphorylated STAT3, protein levels of epithelial‐mesenchymal transition molecular markers and extracellular matrix degradation enzymes were determined through Western blot. We demonstrated that RES could suppress the proliferation and metastatic potential of cervical cancer cells by inactivating phosphorylation of STAT3 at Tyr705 but not Ser727. This effect was intensified by inhibition of the STAT3 signal pathway.

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Tài liệu tham khảo

10.3802/jgo.2018.29.e62

10.1097/MD.0000000000010530

Zhao H, 2019, Effect of neoadjuvant chemotherapy followed by radical surgery for FIGO stage IB2/IIA2 cervical cancer: A multi‐center retrospective clinical study, Medicine (Baltimore), 98, e15604, 10.1097/MD.0000000000015604

Karageorgopoulou S, 2017, Prognostic and predictive factors in patients with metastatic or recurrent cervical cancer treated with platinum‐based chemotherapy, BMC Cancer, 17, 451, 10.1186/s12885-017-3435-x

10.3346/jkms.2006.21.4.683

10.3390/ijms18122589

10.1080/10408398.2016.1263597

10.1016/j.lfs.2018.06.028

10.4161/auto.5.4.7666

10.1097/CEJ.0b013e328360345f

10.1007/s11033-012-1728-3

Zhao Y, 2018, Resveratrol significantly inhibits the occurrence and development of cervical cancer by regulating phospholipid scramblase 1, J Cell Biochem

10.1016/j.bbcan.2013.12.005

Chatterjee K, 2019, Dietary Polyphenols, Resveratrol and Pterostilbene Exhibit Antitumor Activity on an HPV E6‐Positive Cervical Cancer Model: An in vitro and in vivo Analysis, Front Oncol, 9, 352, 10.3389/fonc.2019.00352

10.3390/nu10020243

10.1517/13543780802565791

10.1097/00001813-200507000-00002

10.4062/biomolther.2014.061

10.1002/jcp.22806

10.1186/s13048-015-0152-4

10.3233/CBM-170483

10.1038/srep31672

10.1016/j.phymed.2016.02.011

10.1371/journal.pone.0205918

10.18632/oncotarget.25993

Li D, 2019, Resveratrol suppresses colon cancer growth by targeting the AKT/STAT3 signaling pathway, Int J Mol Med, 43, 630

10.18632/genesandcancer.15

10.1159/000132342

10.1016/0042-6822(87)90478-8

10.3181/00379727-135-35091a

10.1099/0022-1317-80-7-1725

10.1002/jcc.21334

Hong Bin W, 2018, Pterostilbene (3’,5'‐dimethoxy‐resveratrol) exerts potent antitumor effects in HeLa human cervical cancer cells via disruption of mitochondrial membrane potential, apoptosis induction and targeting m‐TOR/PI3K/Akt signalling pathway, J BUON, 23, 1384

10.1021/ci200227u

10.1093/nar/28.1.235

10.1093/nar/gky1004

Belo Y, 2019, Unexpected implications of STAT3 acetylation revealed by genetic encoding of acetyl‐lysine, Biochim Biophys Acta Gen Subj, 10.1016/j.bbagen.2019.05.019

10.1093/nar/gky1033

10.1002/jcc.21256

10.1073/pnas.0609757104

Kang MJ, 2016, Hippocalcin Is Required for Astrocytic Differentiation through Activation of Stat3 in Hippocampal Neural Precursor Cells, Front Mol Neurosci, 9, 110

10.1038/onc.2008.448

10.1038/sj.onc.1206047

10.1002/ijc.25041

10.1016/j.canlet.2017.01.002

Zhu T, 2018, Molecular background of the regional lymph node metastasis of gastric cancer, Oncol Lett, 15, 3409

10.4251/wjgo.v10.i6.124

10.3748/wjg.v22.i8.2434

10.1186/s12885-018-4845-0

10.1038/ncb3478

10.1016/j.canlet.2018.05.016

10.1177/1066896916654763

Zhu GJ, 2018, Role of epithelial‐mesenchymal transition markers E‐cadherin, N‐cadherin, beta‐catenin and ZEB2 in laryngeal squamous cell carcinoma, Oncol Lett, 15, 3472

10.1016/j.ejca.2015.04.021

10.18632/oncotarget.3862

10.4132/KoreanJPathol.2012.46.4.341

10.1097/00001813-200203000-00006

10.1016/j.canlet.2012.10.026

10.18632/oncotarget.3878

10.1038/s41388-019-0906-3

10.18632/oncotarget.4457

Wang DW, 2019, Knockdown of long non‐coding RNA LINC00518 inhibits cervical cancer proliferation and metastasis by modulating JAK/STAT3 signaling, Eur Rev Med Pharmacol Sci, 23, 496

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Cancer Medicine

Tập 9 Số 22

8685-8700

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