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- Title
Impact of ER520, a candidate of selective estrogen receptor modulators, on in vitro cell growth, migration, invasion, angiogenesis and in vivo tumor xenograft of human breast cancer cells.
- Authors
Wang, Lijun; Wang, Ying; Du, Huaqing; Jiang, Yao; Tang, Zhichao; Liu, Hongyi; Xiang, Hua; Xiao, Hong
- Abstract
<bold>Purposes: </bold>ER520, a derivative of indenoisoquinoline, is a patented compound. This study was designed to screen its biological properties and to evaluate its antineoplastic and antiangiogenic effect.<bold>Methods: </bold>Western blot was employed to monitor the ERα and ERβ protein expression in human breast cancer MCF-7 cells and endometrial carcinoma Ishikawa cells. MTT assay was employed to determine cell proliferation. Cell adhesion, scratch and Transwell assay were utilized to estimate the ability of cellular adhesion, migration and invasion. ELISA kit was applied to detect the VEGF products in culture medium. In addition, the inhibitory effect of ER520 on the vessel-like construction of HUVEC cells and the angiogenesis of chicken embryos was investigated. The efficiency of ER520 on tumor growth in nude mice was also assessed.<bold>Results: </bold>ER520 inhibited the expression of ERα in MCF-7 and Ishikawa cells, while it increased ERβ protein level. ER520 also suppressed the proliferation of MCF-7 and Ishikawa cells. Due to its remarkably negative role in cell adhesion, migration and invasion, ER520 showed a potential ability of inhibiting tumor metastasis. Meanwhile, ER520 reduced the VEGF secretion of MCF-7 and Ishikawa cells, prevented the formation of VEGF-stimulated tubular structure and the cell migration of HUVEC cells, and inhibited the angiogenesis of chicken chorioallantoic membrane. Animal experiment also demonstrated that ER520 could frustrate the in vivo tumor growth and the inhibitory ratio was 48.5 % compared with control group.<bold>Conclusion: </bold>Our findings indicate that ER520 possesses the competence to be a candidate against breast cancer and angiogenesis.
- Subjects
SELECTIVE estrogen receptor modulators; CELL growth; CELL migration; NEOVASCULARIZATION; XENOGRAFTS; BREAST cancer treatment; IN vitro studies; PROTEIN metabolism; ANIMALS; ANTHROPOMETRY; BREAST tumors; CANCER invasiveness; CELL culture; CELL lines; CELL physiology; CELL motility; DOSE-effect relationship in pharmacology; EPITHELIAL cells; HYDROCARBONS; ISOQUINOLINE; MICE; MOLECULAR structure; NEOVASCULARIZATION inhibitors; VASCULAR endothelial growth factors; PHARMACODYNAMICS
- Publication
Cancer Chemotherapy & Pharmacology, 2015, Vol 76, Issue 6, p1247
- ISSN
0344-5704
- Publication type
Academic Journal
- DOI
10.1007/s00280-015-2838-0