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卵巢上皮癌组织中hMSH2的表达及其与化疗耐药的关系

张瑾, 李红霞

张瑾, 李红霞. 卵巢上皮癌组织中hMSH2的表达及其与化疗耐药的关系[J]. 肿瘤防治研究, 2015, 42(06): 571-575. DOI: 10.3971/j.issn.1000-8578.2015.06.009
引用本文: 张瑾, 李红霞. 卵巢上皮癌组织中hMSH2的表达及其与化疗耐药的关系[J]. 肿瘤防治研究, 2015, 42(06): 571-575. DOI: 10.3971/j.issn.1000-8578.2015.06.009
ZHANG Jin, LI Hongxia. hMSH2 Expression in Ovarian Epithelial Cancer Tissues and Its Relationship with Chemoresistance[J]. Cancer Research on Prevention and Treatment, 2015, 42(06): 571-575. DOI: 10.3971/j.issn.1000-8578.2015.06.009
Citation: ZHANG Jin, LI Hongxia. hMSH2 Expression in Ovarian Epithelial Cancer Tissues and Its Relationship with Chemoresistance[J]. Cancer Research on Prevention and Treatment, 2015, 42(06): 571-575. DOI: 10.3971/j.issn.1000-8578.2015.06.009

卵巢上皮癌组织中hMSH2的表达及其与化疗耐药的关系

基金项目: 首都卫生发展科研专项项目(首发2011-2008-05)
详细信息
    作者简介:

    张瑾(1982-),女,博士,主治医师,主要从事妇科肿瘤方面的研究

    通讯作者:

    李红霞,E-mail: lihx69@hotmail.com

  • 中图分类号: R737.31

hMSH2 Expression in Ovarian Epithelial Cancer Tissues and Its Relationship with Chemoresistance

  • 摘要: 目的 检测不同化疗敏感程度的卵巢上皮癌组织中hMSH2基因的表达,分析其与化疗耐药及预后的关系。方法 80例新鲜卵巢上皮癌组织均由手术中取得,采用ATP-TCA技术检测卵巢癌组织对八种药物:紫杉醇、卡铂、拓泊替康、多西他赛、吉西他滨、环磷酰胺体内代谢产物、依托泊苷及博来霉素的体外敏感性。采用Real-time PCR及Western blot法分别检测80例卵巢上皮癌组织中hMSH2 基因mRNA和蛋白水平的表达情况。结果 对紫杉醇耐药的卵巢上皮癌组中,hMSH2基因在mRNA及蛋白水平的表达均明显高于敏感组(P<0.01),在对卡铂、拓泊替康、多西他赛耐药组中hMSH2表达水平也明显高于敏感组(P<0.05);hMSH2基因的相对表达值与卡铂、拓泊替康、多西他赛的敏感度系数有显著相关性(P≤0.05)。早期卵巢癌患者组织的hMSH2表达水平明显低于晚期卵巢癌组织(P<0.05)。高、中分化卵巢癌组织hMSH2蛋白表达水平明显低于低分化卵巢癌组织(P=0.000)。原发卵巢癌患者组织的hMSH2表达水平明显低于复发卵巢癌患者组织(P<0.01)。结论 hMSH2基因的高表达与卵巢癌化疗耐药及预后相关,化疗可能诱导hMSH2基因的高表达;下调hMSH2基因的表达或许是逆转肿瘤耐药的新途径。

     

    Abstract: Objective To examine hMSH2 expression in ovarian epithelial cancer tissues with different chemosensitivity, and to investigate the association between hMSH2 expression and chemoresistance. Methods Tissues were collected from 80 patients who underwent cytoreductive surgery. Viable ovarian cancer cells obtained from malignant tissues were tested for the sensitivity to paclitaxel, carboplatin, topotecan, gemcitabine, docetaxel, etoposide, bleomycin and 4-hydroperoxycyclophosphamide using ATP-TCA. The expression levels of hMSH2 mRNA and protein in 80 cases of ovarian carcer tissues were determined by real-time PCR and Western blot assay. Results There were significant differences of hMSH2 mRNA and protein expression in epithelial ovarian cancer tissues. The resistance to paclitaxel group showed higher hMSH2 expression at both mRNA and protein levels than the sensitive one (P<0.01). The same results were detected in carboplatin, docetaxel and topotecan groups(P<0.05). The expression levels of hMSH2 were correlated with the sensitivity indexes to docetaxel, topotecan and carboplatin (P≤0.05). The early-stage (Ⅰ, Ⅱ) ovarian epithelial cancer tissues showed lower hMSH2 expression than advanced-stage (Ⅲ) ones(P<0.05). The well- to morderate-differentiated ovarian epithelial cancer tissues showed lower hMSH2 expression at protein levels than the poor-differentiated ones (P=0.000). Primary ovarian epithelial cancer tissues showed lower hMSH2 expression than the recurrent ones (P<0.01). Conclusion hMSH2 overexpression is correlated to chemotherapy resistance and poor prognosis of ovarian cancer. Chemotherapy could induce high expression of hMSH2. Down-regulating hMSH2 expression may be a new method in ovarian cancer therapy.

     

  • [1] Li HX, Guan XY, Zhang SM, et al. Study on the relationship of taxol-resistance of ovarian carcinoma with the amplification of 2p 22 on chromosome and the expression of hmsh2 gene[J]. Zhong Liu Fang Zhi Yan Jiu, 2006, 33(8): 565-7. [李红霞, 关兴元, 张 素梅, 等. 染色体2p22的过度扩增及hmsh2基因的高表达与卵 巢癌紫杉醇耐药相关性的研究[J]. 肿瘤防治研究, 2006, 33(8): 56 5-7.]
    [2] Wang AX, Li J, Li H. Study on RNA interference silencing hMSH2 induces the reversal chemo-resistance of ovarian carcinoma cell line OC3/TAX300[J]. Zhonghua Fu Chan Ke Za Zhi, 2014, 49(3): 21 3-7. [王爱新, 李健, 李红霞. 沉默hMSH2基因表达对紫杉醇 耐药的卵巢上皮性癌OC3/TAX300细胞耐药性的影响[J]. 中华 妇产科杂志, 2014, 49(3): 213-7.]
    [3] Zhang W. Clinical application of in vitro drug sensitivity assay for tumor using ATP-TCA[J]. Ai Zheng Jin Zhan, 2005, 3(5): 427-35. [张伟. 生物荧光肿瘤体外药敏检测技术的临床应用及其探讨 [J] 癌症进展, 2005, 3(5): 427-35.]
    [4] Zhao D, Zhang W, Li XG, et al. Predicting clinical chemosensitivity of primary ovarian cancer using adenosine triphosphate-tumor chemosensitivity assay combined with detection of drug resistance genes[J]. Zhonghua Fu Chan Ke Za Zhi, 2011, 46(3): 193-8. [赵丹, 张伟, 李晓光, 等. 三磷酸腺苷- 肿瘤体外药敏试验联合耐药基因检测预测原发性卵巢癌的化 疗敏感性[J]. 中华妇产科杂志, 2011, 46(3): 193-8.]
    [5] Chang QY, Wu LY, Li XG, et al. Cost-effectiveness of adenosine triphosphate-tumor chemosensitivity assay in advanced epithelial ovarian cancer chemotherapy[J]. Ai Zheng Jin Zhan, 2011, 9(2): 19 1-5,216. [常青云, 吴令英, 李晓光, 等. 三磷酸腺苷-肿瘤体外 药敏检测在晚期卵巢上皮癌化疗中的成本-效果评价[J]. 癌症 进展, 2011, 9(2): 191-5,216. ]
    [6] Neubauer H, Stefanova M, Solomayer E, et al. Predicting resistance to platinum-containing chemotherapy with the ATP tumor chemosensitivity assay in primary ovarian cancer[J]. Anticancer Res, 2008, 28(2A): 949-55.
    [7] Marcelis CL, van der Putten HW, Tops C, et al. Chemotherapy resistant ovarian cancer in carriers of an hMSH2 mutation?[J]. Fam Cancer, 2001, 1(2): 107-9.
    [8] Gu GL, Zhu XQ, Wei XM, et al. Epithelial-mesenchymal transition in colorectal cancer tissue of patients with Lynch syndrome[J]. World J Gastroenterol, 2014, 20(1): 250-7.
    [9] Masuda K, Banno K, Hirasawa A, et al. Relationship of lower uterine segment cancer with Lynch syndrome: a novel case with an hMLH1 germline mutation[J]. Oncol Rep, 2012, 28(5): 15 37-43.
    [10] Yasin SL, Rainbow AJ. A combination of MSH2 DNA mismatch repair deficiency and expression of the SV40 large T antigen results in cisplatin resistance of mouse embryonic fibroblasts[J]. Int J Oncol, 2011, 39(3): 719-26.
    [11] Materna V, Surowiak P, Markwitz E, et al. Expression of factors involved in regulation of DNA mismatch repair- and apoptosis pathways in ovarian cancer patients[J]. Oncol Rep, 2007, 17(3): 50 5-16.
    [12] Vageli DP, Zaravinos A, Daniil Z, et al. hMSH2 and hMLH1 gene expression patterns differ between lung adenocarcinoma and squamous cell carcinoma: correlation with patient survival and response to adjuvant chemotherapy treatment[J]. Int J Biol Markers, 2013, 27(4): e400-4.
    [13] Li SN, Li L, Wang CZ. Expressions of hMSH2 and MGMT proteins in endometrial caicinoma[J]. Dalian Yi Ke Da Xue Xue Bao, 2011, 33(5): 430-3. [李斯宁, 李玲, 王长智. hMSH2、 MGMT在子宫内膜癌中的表达及其病理意义[J]. 大连医科大 学学报, 2011, 33(5): 430-3.]
    [14] Nadin SB, Vargas-Roig LM, Drago G, et al. DNA damage and repair in peripheral blood lymphocytes from healthy individuals and cancer patients: a pilot study on the implications in the clinical response to chemotherapy[J]. Cancer Lett, 2006, 239(1): 84 -97.
    [15] Steffensen KD, Smoter M, Waldstrøm M, et al. Resistance to first line platinum paclitaxel chemotherapy in serous epithelial ovarian cancer: The prediction value of ERCC1 and Tau expression[J]. Int J Oncol, 2014, 44(5): 1736-44.
    [16] Li QQ, Lee RX, Liang H, et al. β-Elemene enhances susceptibility to cisplatin in resistant ovarian carcinoma cells via downregulation of ERCC-1 and XIAP and inactivation of JNK[J]. Int J Oncol, 20 13, 43(3): 721-8.
    [17] Mohammed MZ, Vyjayanti VN, Laughton CA, et al. Development and evaluation of human AP endonuclease inhibitors in melanoma and glioma cell lines[J]. Br J Cancer, 2011, 104(4): 653-63.
    [18] Syrios J, Banerjee S, Kaye SB. Advanced epithelial ovarian cancer: from standard chemotherapy to promising molecular pathway targets-where are we now?[J]. Anticancer Res, 2014, 34 (5): 2069-77.
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出版历程
  • 收稿日期:  2014-09-09
  • 修回日期:  2014-12-18
  • 刊出日期:  2015-06-24

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