标题:Determination of the migration effect and molecular docking of verteporfin in different subtypes of breast cancer cells
作者:WEI C.; LI X.
作者机构:[WEI, C] Department of The First Clinical Medical School, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, z250355, China;[ LI, X 更多
通讯作者:LI, X(drlixqi@hotmail.com)
通讯作者地址:[LI, X] Department of Breast surgery, Second Affiliated Hospital of Shandong First Medical University, 366 Taishan Road, China;
来源:Molecular Medicine Reports
出版年:2020
卷:22
期:5
页码:3955-3961
DOI:10.3892/mmr.2020.11482
关键词:Inhibitor; Migration; Non-photoinduced therapy; Verteporfin; Yes-associated protein; Yes-associated protein/transcriptional enhanced associate domain complex
摘要:Breast cancer is one of the most aggressive malignant tumors in women. According to the expression differences of estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 (HER- 2) and cell proliferation antigen Ki-67, breast cancer can be divided into four molecular subtypes: Luminal A, Luminal B, HER- 2 overexpression and Basal-like. Yes-associated protein (YAP), a downstream effector of the Hippo pathway, is overexpressed in human cancers and is associated with proliferation, apoptosis, migration, invasion and resistance to chemotherapy drugs in breast cancer cells. Verteporfin (VP) is used as a photosensitizer in the treatment of neovascular macular degeneration. VP is also identified as an inhibitor of YAP/TEA domain transcription factor (TEAD ) interaction in the absence of light activation. However, detailed structural information about VP and YAP interactions is relatively scarce and VP research targeting YAP in different molecular subtypes of breast cancer cells is also rare. The aims of the present study were to structurally describe the VP binding site in the YAP crystal structure and to verify the non-photoreactive VP effect targeting YAP on the migration of different molecular subtypes of breast cancer cells. The crystal structure of VP and YAP was calculated by AutoDock 4.2 and the result was illustrated using PyMOL . The non-photoactivated VP effect on the migration of Luminal A MCF-7, Luminal B BT-474 and triple-negative breast cancer BT-549 breast cancer cells was evaluated by wound healing and Transwell migration experiments. Results from molecular docking experiments demonstrated that VP could interact through hydrogen bonds and hydrophobic interactions with important YAP residues involved in TEAD s binding (Gln82, Val84, Met86 and Arg89). Migration experiments revealed that the non-photoinduced VP could inhibit the migration of different molecular subtypes of breast cancer cells. The results of the present study indicated that VP may be a novel repositioned drug for breast cancer treatment in the future. © 2020 Spandidos Publications. All rights reserved.
收录类别:SCOPUS
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85091887794&doi=10.3892%2fmmr.2020.11482&partnerID=40&md5=77731fcfc6907c859619f8ef69b62812
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