title: Curcumin inhibits LPA-induced invasion by attenuating RhoA/ROCK/MMPs pathway in MCF7 breast cancer cells.
abstract: Breast cancer generally shows poor prognosis because of its invasion and metastasis. Lysophosphatidic acid (LPA) induces and aggravates cancer invasion and metastasis by activating its downstream signal pathways. RhoA/ROCK/MMP signaling was found one of the LPA-induced pathways, which may be involved in invasion of breast cancer. Furthermore, we investigated whether this pathway was involved in curcumin's effect against LPA-induced invasion. LPA incubation was used to enhance invasion of MCF-7 breast cancer cells. RhoA expression was knocked-down by siRNA technique. MTT assay was used to evaluate the proliferation. Transwell assay was utilized to investigate the invasion ability of MCF-7 cells. Real-time PCR and Western blotting were used to assess the expressions of RhoA, ROCK1, ROCK2, MMP2 and MMP9 at both translational and transcriptional levels. The RhoA and ROCK activities were also evaluated. LPA incubation significantly boosted invasion rate of MCF-7. RhoA silencing by siRNA dramatically inhibited LPA-enhanced invasion. Concurrently, RhoA and ROCK activities and expression levels of RhoA, ROCK1, ROCK2, MMP2 and MMP9 were down-regulated by RhoA siRNA transfection. In order to avoid influence of cytotoxicity of curcumin, concentrations below 45 μmol/L were selected to further investigate the mechanism of curcumin's anti-invasion effect. Invasion of LPA-incubated MCF-7 cells was impaired by curcumin in a concentration-dependent manner. Concurrently, RhoA and ROCK activities and expression levels of RhoA, ROCK1, ROCK2, MMP2 and MMP9 were down-regulated by curcumin in a concentration-dependent manner. In conclusion, RhoA/ROCK/MMPs pathway activation is involved in LPA-induced invasion in MCF-7 cells; curcumin inhibited LPA-induced invasion in MCF-7 cells by attenuating RhoA/ROCK/MMPs pathway.
authors.affiliation: The Second Department of Thoracic Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.affiliation: Department of Nuclear Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Duan
authors.affiliation: The Second Department of Thoracic Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.|Department of Anesthesia, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Cai
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Lanzhou University, Lanzhou, Gansu, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Liu
authors.affiliation: The Second Department of Thoracic Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Yang
authors.affiliation: The Second Department of Thoracic Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pathology, Lanzhou University Medical School, Lanzhou, Gansu, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The Second Department of Thoracic Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China. wangjsh@mail.xjtu.edu.cn.
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008246:Lysophospholipids / Q000009:adverse effects*; D061986:MCF-7 Cells; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D015398:Signal Transduction / Q000187:drug effects*; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D008246:Lysophospholipids; C066737:RHOA protein, human; D054460:rho-Associated Kinases; D020782:Matrix Metalloproteinases; D020742:rhoA GTP-Binding Protein; D003474:Curcumin; C032881:lysophosphatidic acid
keywords: Breast cancer; Curcumin; Invasion; Lysophosphatidic acid