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山东大学学报(医学版) ›› 2016, Vol. 54 ›› Issue (3): 24-29.doi: 10.6040/j.issn.1671-7554.0.2015.359

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CXXC4增强上皮性卵巢癌细胞对化疗药物的敏感性

赵云霞,宋静,张灿灿,林雪艳,尉蔚,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:2015-04-08 出版日期:2016-03-10 发布日期:2016-03-10
  • 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(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)

CXXC4 promotes sensitivity to chemotherapy drugs in epithelial ovarian cancer cells

ZHAO Yunxia, SONG Jing, ZHANG Cancan, LIN Xueyan, WEI Wei, TIAN Yongjie   

  1. Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China
  • Received:2015-04-08 Online:2016-03-10 Published:2016-03-10

摘要: 目的 探讨CXXC4对卵巢癌细胞的增殖及药物敏感性的影响。 方法 采用Western blotting和Real-time PCR分别从蛋白水平和mRNA水平检测正常卵巢上皮细胞和卵巢癌细胞中的CXXC4表达,脂质体法将重组质粒pcDNA3-CXXC4和siRNA-CXXC4分别转染人卵巢癌细胞SKOV3、Caov3和正常卵巢上皮细胞IOSE80,CCK8法分析CXXC4对细胞增殖及药物敏感性的影响。 结果 与正常卵巢上皮细胞相比,卵巢癌细胞中CXXC4低表达,外源性CXXC4过表达抑制卵巢癌细胞SKOV3、Caov3的增殖能力,以及增强肿瘤细胞对化疗药物的敏感性;降低CXXC4的表达能促进正常卵巢上皮细胞的增殖能力,促进细胞对化疗药物的耐受。 结论 CXXC4的过表达抑制卵巢癌细胞的增殖能力,且增强肿瘤细胞对化疗药物的敏感性,提示其可能作为一个潜在的卵巢癌疗效预测标记物以及化疗增敏的分子靶点。

关键词: CXXC4, 卵巢癌, 耐药, 增殖

Abstract: Objective To explore the effect of CXXC4 on the proliferation and sensitivity to chemotherapy drugs in ovarian carcinoma cells. Methods Protein and mRNA levels of CXXC4 were detected in nomal ovarian epithelial cells and ovarian carcinoma cells by Western blotting and Real-time PCR, respectively. The recombinant plasmid pcDNA3-CXXC4 and siRNA-CXXC4 were transfected into SKOV3, Caov3 cells and IOSE80 cells via Lipo2000. CCK8 assay was used to evaluate the effect of CXXC4 on the proliferation and sensitivity to chemotherapy drugs. Results Compared with the normal ovarian epithelial cells, CXXC4 expression was lower in ovarian carcinoma cells. Overexpression of CXXC4 inhibited the proliferation capacity and increased the sensitivity to chemotherapy drugs in SKOV3 and Caov3 cells. Decreased CXXC4 expression could promote the proliferation capacity and the chemo-resistance to chemotherapy drugs of normal ovarian epithelial cells. Conclusion Overexpression of CXXC4 could inhibit the proliferation capacity and increase the sensitivity to chemotherapy drugs in ovarian carcinoma cells, suggesting it would be a potential biomarker to predict the efficacy or a molecular target to enhance the efficacy to chemotherapy in ovarian carcinoma cells.

Key words: Ovarian cancer, Chemo-resistance, CXXC4, Proliferation

中图分类号: 

  • R737.31
[1] Jemal A, Bray F, Center MM, et al. Global cancer statistics [J]. CA Cancer J Clin, 2011, 61(2):69-90.
[2] 陈万青,张思维,曾红梅,等.中国2010年恶性肿瘤发病与死亡[J].中国肿瘤, 2014, 23(1):1-10. CHEN Wanqing, ZHANG Siwei, ZENG Hongmei, et al. Report of cancer incidence and mortality in China, 2010[J]. China Cancer, 2014, 23(1):1-10.
[3] Jelovac D, Armstrong DK. Recent progress in the diagnosis and treatment of ovarian cancer[J]. CA Cancer J Clin, 2011, 61(3):183-203.
[4] Vergote I, Trope CG, Amant F, et al. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer[J]. N Engl J Med, 2010, 363(10):943-953.
[5] Cannistra SA. Cancer of the ovary[J]. N Engl J Med, 2004, 351(24):2519-2529.
[6] Ledermann JA, Raja FA, Fotopoulou C, et al. Newly diagnosed and relapsed epithelial ovarian carcinoma:ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up[J]. Ann Oncol, 2013, 24(Suppl 6):vi24-vi32.
[7] Jemal A, Siegel R, Xu J, et al. Cancer statistics[J]. CA Cancer J Clin, 2010, 60(5):277-300.
[8] Hino S, Kishida S, Michiue T, et al. Inhibition of the Wnt signaling pathway by Idax, a novel Dvl-binding protein[J]. Mol Cell Biol, 2001, 21(1):330-342.
[9] Michiue T, Fukui A, Yukita A, et al. XIdax, an inhibitor of the canonical Wnt pathway, is required for anterior neural structure formation in Xenopus [J]. Dev Dyn, 2004, 230(1):79-90.
[10] Kojima T, Shimazui T, Hinotsu S, et al. Decreased expression of CXXC4 promotes a malignant phenotype in renal cell carcinoma by activating Wnt signaling [J]. Oncogene, 2009, 28(2):297-305.
[11] Colombo PE, Fabbro M, Theillet C, et al. Sensitivity and resistance to treatment in the primary management of epithelial ovarian cancer [J]. Crit Rev Oncol/Hematol, 2014, 89(2):207-216.
[12] Thigpen T. A rational approach to the management of recurrent or persistent ovarian carcinoma [J]. Clin Obstet Gynecol, 2012, 55(1):114-130.
[13] Abada P, Howell SB. Regulation of Cisplatin cytotoxicity by cu influx transporters [J]. Metal Based Drugs, 2010:317581. doi:10.1155/2010/317581.
[14] Helleman J, van Staveren IL, Dinjens WN, et al. Mismatch repair and treatment resistance in ovarian cancer [J]. BMC Cancer, 2006, 6:201.
[15] Surowiak P, Materna V, Kaplenko I, et al. Augmented expression of metallothionein and glutathione S-transferase pi as unfavourable prognostic factors in cisplatin-treated ovarian cancer patients[J]. Virchows Arch, 2005, 447(3):626-633.
[16] Kobayashi Y, Seino K, Hosonuma S, et al. Side population is increased in paclitaxel-resistant ovarian cancer cell lines regardless of resistance to cisplatin[J]. Gynecol Oncol, 2011, 121(2):390-394.
[17] Hu L, McArthur C, Jaffe RB. Ovarian cancer stem-like side-population cells are tumourigenic and chemoresistant[J]. Br J Cancer, 2010, 102(8):1276-1283.
[18] Wang QE, Han C, Milum K, et al. Stem cell protein Piwil2 modulates chromatin modifications upon cisplatin treatment[J]. Mutat Res, 2011, 708(1-2):59-68.
[19] Alvero AB, Chen R, Fu HH, et al. Molecular phenotyping of human ovarian cancer stem cells unravels the mechanisms for repair and chemoresistance[J]. Cell Cycle, 2009, 8(1):158-166.
[20] Kurrey NK, Jalgaonkar SP, Joglekar AV, et al. Snail and slug mediate radioresistance and chemoresistance by antagonizing p53-mediated apoptosis and acquiring a stem-like phenotype in ovarian cancer cells[J]. Stem Cells, 2009, 27(9):2059-2068.
[21] Lu H, Sun J, Wang F, et al. Enhancer of zeste homolog 2 activates wnt signaling through downregulating CXXC finger protein 4[J]. Cell Death Dis, 2013, 4:e776. doi:10.1038/cddis.2013.293.
[22] Lu H, Jin W, Sun J, et al. New tumor suppressor CXXC finger protein 4 inactivates mitogen activated protein kinase signaling[J]. FEBS Lett, 2014, 588(18):3322-3326.
[23] Arend RC, Londono-Joshi AI, Straughn JM, et al. The Wnt/beta-catenin pathway in ovarian cancer:a review [J]. Gynecol Oncol, 2013, 131(3):772-779.
[24] Fan HY, Liu Z, Mullany LK, et al. Consequences of RAS and MAPK activation in the ovary:the good, the bad and the ugly [J]. Mol Cell Endocrinol, 2012, 356(1-2):74-79.
[25] Grendys EC, Wang D, Tian C, et al. Overview of a chemoresponse assay in ovarian cancer [J]. Clin Transl Oncol, 2014, 16(9):761-769.
[26] Han Y, Huang H, Xiao Z, et al. Integrated analysis of gene expression profiles associated with response of platinum/paclitaxel-based treatment in epithelial ovarian cancer [J]. PloS One, 2012, 7(12):e52745. doi:10.1371/journal.pone.0052745.
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