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1-calcium phosphate-uracil inhibits intraperitoneal metastasis by suppressing FAK in epithelial ovarian cancer

机译:1-磷酸钙 - 尿嘧啶通过抑制上皮卵巢癌中的FAK而抑制腹膜内转移

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摘要

The high mortality of epithelial ovarian cancer (EOC) is primarily due to vast intraperitoneal dissemination. 1-calcium phosphate-uracil (1-CP-U) has previously shown the function of inhibiting migration and invasion in multiple tumor cell lines. In this study, we further assessed the possible role of 1-CP-U in suppressing the peritoneal metastasis of EOC cells. First, we demonstrated that 1-CP-U had an inhibitory effect on EOC cells in cell-matrix adhesion, migration and invasion assay in vitro. Within the in vivo model, animals were intraperitoneally inoculated with SKOV3-Luc cells and then 1-CP-U intraperitoneal (i.p.) injection was performed every 5 d for a total of 3 wk. At the 7th d, omenta from each group were analyzed with luciferase activity and bioluminescence imaging assay, which showed a significant reduction of luciferase activity in the omenta from 1-CP-U group. In addition, the rest mice continued treatment and consistent detection of bioluminescence imaging. The data indicated that intraperitoneal metastatic nodules were less-developed in 1-CP-U group. Peritoneal metastatic tumor nodules were detected for immunofluorescent staining, which showed a reduction in FAK and p-FAK staining with 1-CP-U treatment group. Meanwhile, expressions of FAK and its downstream signaling were detected by western blot in tumor tissues and EOC cell lines, which showed significant decreases in the 1-CP-U treatment group. In conclusion, 1-CP-U had a profound inhibitory effect on adhesion, invasion and metastasis of EOC in vitro and suppressed intraperitoneal dissemination and cancer growth in vivo assay, which was associated with inhibition on the FAK pathway.
机译:上皮性卵巢癌(EOC)的高死亡率主要是由于大幅腹膜内传播。磷酸钙 - 尿嘧啶(1-CP-U)先前已经示出了抑制多种肿瘤细胞系中的迁移和侵袭的功能。在这项研究中,我们进一步评估了1-CP-U抑制EOC细胞腹膜转移的可能作用。首先,我们证明,1-CP-U对体外细胞 - 基质粘附,迁移和侵袭测定的EOC细胞对EC细胞进行了抑制作用。在体内模型中,使用Skov3-Luc细胞腹膜内接种,然后每5 d进行1-Cp-U腹膜内(I.P.)注射,共3W。在第7天,用荧光素酶活性和生物发光成像测定分析来自每组的Omenta,其显示出从1-CP-U组的Omenta中的荧光素酶活性显着降低。此外,其余小鼠继续治疗和一致地检测生物发光成像。数据表明,在1-CP-U组中较少开发的腹腔转移性结节。检测到免疫荧光染色的腹膜转移性肿瘤结节,其表现出用1-CP-U处理组的FAK和P-FAK染色。同时,通过肿瘤组织和EOC细胞系中的蛋白质印迹检测到FAK及其下游信号的表达,其在1-CP-U治疗组中显示出显着降低。总之,1-CP-U对体外粘附,侵袭和转移具有深远的抑制作用,并抑制了体内测定中的腹腔传播和癌症生长,这与对FAK途径的抑制相关。

著录项

  • 来源
    《Cell cycle》 |2019年第16期|共13页
  • 作者单位

    Tongji Univ Shanghai First Matern &

    Infant Hosp Dept Obstet &

    Gynecol Sch Med Shanghai Peoples;

    Tongji Univ Shanghai First Matern &

    Infant Hosp Dept Obstet &

    Gynecol Sch Med Shanghai Peoples;

    Tongji Univ Shanghai First Matern &

    Infant Hosp Dept Obstet &

    Gynecol Sch Med Shanghai Peoples;

    Tongji Univ Shanghai First Matern &

    Infant Hosp Dept Obstet &

    Gynecol Sch Med Shanghai Peoples;

    Tongji Univ Shanghai First Matern &

    Infant Hosp Dept Obstet &

    Gynecol Sch Med Shanghai Peoples;

    Tongji Univ Shanghai First Matern &

    Infant Hosp Dept Obstet &

    Gynecol Sch Med Shanghai Peoples;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;
  • 关键词

    1-calcium phosphate-uracil; FAK; EOC; adhesion; metastasis;

    机译:1-磷酸钙 - 尿嘧啶;FAK;EOC;粘附;转移;

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