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山东大学学报(医学版) ›› 2015, Vol. 53 ›› Issue (7): 1-7.doi: 10.6040/j.issn.1671-7554.0.2015.171

• 基础医学 •    下一篇

HGF/PARP-1信号通路调控卵巢癌细胞侵袭转移的作用

吕树卿, 尉蔚, 张灿灿, 田永杰   

  1. 山东大学附属省立医院妇产科, 山东 济南 250021
  • 收稿日期:2015-02-10 修回日期:2015-04-24 出版日期:2015-07-10 发布日期:2015-07-10
  • 通讯作者: 田永杰。E-mail:tianyongjie@sdu.edu.cn E-mail:tianyongjie@sdu.edu.cn
  • 基金资助:
    国家自然科学基金应急管理项目(81441075);山东省自然科学基金(ZR2014HM108);山东省自然科学基金青年项目(ZR2013HQ030)

Mechanism of HGF/PARP-1 signaling pathway regulating invasion and metastasis of ovarian cancer

LÜ Shuqing, WEI Wei, ZHANG Cancan, TIAN Yongjie   

  1. Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China
  • Received:2015-02-10 Revised:2015-04-24 Online:2015-07-10 Published:2015-07-10

摘要: 目的 观察聚腺苷酸二磷酸核糖聚合酶-1(PARP-1)在肝细胞生长因子(HGF)诱导的卵巢癌细胞侵袭转移中的作用及相关信号转导通路。方法 Transwell实验检测不同浓度HGF对卵巢癌SKOV-3细胞体外侵袭力的影响;实时荧光定量PCR、Western blotting检测不同浓度及作用时间HGF对SKOV-3细胞PARP-1mRNA及蛋白表达的影响;RNA干扰沉默SKOV-3细胞的PARP-1基因, 按不同处理因素将SKOV-3细胞分为空白对照组、HGF组、PARP-siRNA组、HGF+PARP-siRNA组;NC-siRNA组、HGF+NC-siRNA组。Western blotting检测不同处理组细胞内PARP-1蛋白表达。Transwell实验检测各组细胞侵袭力。ELISA法检测各组细胞上清中基质金属蛋白酶-2(MMP-2)的含量。结果 HGF可明显促进SKOV-3细胞的体外侵袭能力, 并呈浓度时间依赖性。40 ng/mL HGF作用24 h后, HGF可明显上调SKOV-3细胞中PARP-1的表达水平;PARP-siRNA组细胞PARP-1的表达低于NC-siRNA组(P<0.05), 干扰PARP-1的表达降低了HGF对SKOV-3细胞侵袭力及MMP-2含量的影响。结论 HGF可促进卵巢癌SKOV-3细胞的侵袭转移, 其作用机制可能与PARP-1介导的MMP-2表达增加有关。

关键词: 基质金属蛋白酶-2, 卵巢肿瘤, 侵袭, 聚腺苷酸二磷酸核糖聚合酶-1, 肝细胞生长因子

Abstract: Objective To investigate the effects and signaling pathway of HGF-regulated PARP-1 expression on invasion and metastasis of ovarian cancer. Methods SKOV-3 cells were incubated with various concentrations of HGF to examine their invasive abilities by Transwell assay. Relative expression of PARP-1 after HGF treatment in SKOV-3 cells was analyzed by RT-PCR and Western blotting. SKOV3 cells were transfected with either negative control siRNA (NC-siRNA group) or PARP-1 siRNA (PARP1-siRNA group), and divided into different groups depending on different factors: blank control group; HGF group; PARP-siRNA group; HGF+PARP-siRNA group; NC-siRNA group; HGF+NC-siRNA group. The expression of PARP-1 in different groups was measured with Western blotting. The invasive abilities were examined with Transwell assay. The expression of MMP-2 was detected with ELISA. Results HGF promoted cell invasion in a concentration- and time-dependent manner in the SKOV-3 cell line. The expression of PARP-1 in SKOV-3 cells increased after HGF 40 ng/mL treatment for 24 hours. The expression of PARP-1 in PARP1-siRNA group was lower than that in NC-siRNA group (P<0.05). The transfection significantly reduced impacts of HGF on SKOV-3 cell invasion and the expression of MMP-2. Conclusion HGF promotes the invasion and metastasis of ovarian cancer. This effect may be related to the increased expression of MMP-2 which is mediated by PARP-1.

Key words: Invasion, Matrix metalloproteinase-2, Hepatocyte growth factor, Ovarian neoplams, Poly (ADP-ribose) polymerase-1

中图分类号: 

  • R737.31
[1] Desai A, Xu J, Aysola K, et al. Epithelial ovarian cancer: an overview[J]. World J Transl Med, 2014, 3(1): 1-8.
[2] Kawaguchi M, Kawaka H. Mechanisms of hepatocyte growth factor activation in cancer tissues[J]. Cancers (Basel), 2014, 6(4): 1890-1904.
[3] Hung CM, Kuo DH, Chou CH, et al. Osthole suppresses hepatocyte growth factor (HGF)-induced epithelial-mesenchymal transition via repression of the c-Met/Akt/mTOR pathway in human breast cancer cells[J]. J Agric Food Chem, 2011, 59(17): 9683-9690.
[4] Zhang J, Kan Y, Tian Y, et al. Effect of poly (ADP-ribosyl) polymerase (PARP) inhibitor on cisplatin resistance & proliferation of the ovarian cancer C13* cells[J]. Indian J Med Res, 2013, 137(3): 527-532.
[5] Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation[J]. Cell, 2011, 144(5): 646-674.
[6] Wei W, Kong B, Yang Q, et al. Hepatocyte growth factor enhances ovarian cancer cell invasion through downregulation of thrombospondin-1[J]. Cancer Biol Ther, 2010, 9(2): 79-87.
[7] Parikh RA, Wang P, Beumer JH, et al. The potential roles of hepatocyte growth factor (HGF)-MET pathway inhibitors in cancer treatment[J]. Onco Targets Ther, 2014, 7: 969-983. doi: 10.2147/OTT.S40241. eCollection 2014.
[8] Koh SA, Kim MK, Lee KH, et al. RhoGDI2 is associated with HGF-mediated tumor invasion through VEGF in stomach cancer[J]. Clin Exp Metastasis, 2014, 31(7): 805-815.
[9] Nagai T, Arao T, Furuta K, et al. Sorafenib inhibits the hepatocyte growth factor-mediated epithelial mesenchymal transition in hepatocellular carcinoma[J]. Mol Cancer Ther, 2011, 10(1): 169-177.
[10] García-Parra J, Dalmases A, Morancho B, et al. Poly (ADP-ribose) polymerase inhibition enhances trastuzumab antitumour activity in HER2 overexpressing breast cancer[J]. Eur J Cancer, 2014, 50(15): 2725-2734.
[11] 李中林, 梅鹏金, 白津, 等. 乳腺癌转移抑制基因1通过金属蛋白酶组织抑制因子-2/基质金属蛋白酶-2途径抑制胶质瘤细胞侵袭[J]. 中华实验外科杂志, 2013, 30(11): 2327-2329. LI Zhonglin, MEI Pengjin, BAI Jin, et al. Breast cancer metastasis suppressor-1 inhibits human glioma cells invasion by tissue inhibitor of metalloproteinase-2/matrix metalloproteinase-2 pathway[J]. Chin J Exp Surg, 2013, 30(11): 2327-2329.
[12] Rodriguez MI, Peralta-Leal A, O'Valle F, et al. PARP-1 regulates merastatic melanoma through modulation of vimentin-induced maligant transformation[J]. PLoS Genet, 2013, 9(6): 1-14.
[13] Gao N, Tian JX, Shang YH, et al. Catalpol suppresses proliferation and facilitates apoptosis of OVCAR-3 ovarian cancer cells through upregulating microRNA-200 and downregulating MMP-2 expression[J]. Int J Mol Sci, 2014, 15(11): 19394-19405.
[14] Jaafar H, Sharif SE, Murtey MD. Pattern of collagen fibers and localization of matrix metalloproteinase 2 and 9 during breastcancer invasion[J]. Tumori, 2014, 100(5): e204-211.
[15] Mariani M, McHugh M, Petrillo M, et al. HGF/c-Met axis drives cancer aggressiveness in the neo-adjuvant setting of ovarian cancer[J]. Oncotarget, 2014, 5(13): 4855-4867.
[16] Matsui S, Osada S, Tomita H, et al. Clinical significance of aggressive hepatectomy for colorectal liver metastasis, evaluated from the HGF/c-Met pathway[J]. Int J Oncol, 2010, 37(2): 289-297.
[17] Ramanujum R, Lin YL, Liu JK, et al. Regulatory expression of MMP-8/MMP-9 and inhibition of proliferation, migration and invasion in human lung cancer A549 cells in the presence of HGF variants[J]. Kaohsiung J Med Sci, 2013, 29(10): 530-539.
[18] Kim J, Pyun JA, Cho SW, et al. Lymph node metastasis of gastric cancer is associated with the interaction between poly (ADP-ribose) polymerase 1 and matrix metallopeptidase 2[J]. DNA Cell Biol, 2011, 30(12): 1011-1017.
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