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中国癌症防治杂志 ›› 2013, Vol. 5 ›› Issue (3): 221-227.doi: 10.3969/j.issn.1674-5671.2013.03.07

• 临床研究 • 上一篇    下一篇

端粒酶与卵巢上皮性癌化疗的相关性研究

  

  1. 1深圳市龙华区人民医院妇产科;2广西医科大学附属肿瘤医院妇瘤科;3深圳宝安区妇幼保健院保健科
  • 出版日期:2013-09-25 发布日期:2013-10-10
  • 通讯作者: 黎丹戎 E-mail:danronli@163.com

Association between telomerase activity and chemotherapy in ovarian epithelial cancer

  • Online:2013-09-25 Published:2013-10-10

摘要: 目的 检测卵巢上皮性癌患者化疗前后端粒酶活性的变化,探讨以顺铂为主的联合化疗对卵巢癌端粒酶活性的抑制作用。方法 43例原发性卵巢上皮性癌患者行首次卵巢癌细胞减灭+淋巴结清扫术,采用 TRAP-PCR-银染法测定癌组织的端粒酶活性;RT-PCR法测定hTERT基因的表达;抗生素-生物素过氧化酶复合物(SP)免疫组化法检测hTERT蛋白的表达。术后予顺铂+环磷酰胺(A组)、顺铂+紫杉醇(B组)、顺铂+环磷酰胺+多柔比星(C组)全身化疗6.5(6~8)个疗程,选取临床检查和影像学检查未发现肿瘤残存、血液CA125水平在正常范围者30例(A组13例,B组11例,C组6例)行二次探查术,术中取原病灶周围组织活检,测定其端粒酶活性、hTERT基因及其蛋白的表达变化。随访3组患者的5年生存率。结果 43例卵巢上皮性癌患者化疗前端粒酶活性的高低与病理类型、病理分级、FIGO分期无关,差异无统计学意义(P>0.05)。化疗后3组化疗方案均有下调端粒酶活性的作用,化疗前后端粒酶活性阳性率分别为88.37%、36.67%,差异有统计学意义(P<0.05),其中B组下调端粒酶hTERT蛋白的表达较明显(P<0.05)。化疗后hTERT蛋白的表达较化疗前明显下调 (P<0.05),但患者5年生存率无明显提高(P>0.05)。 结论 卵巢上皮性癌以顺铂为主的联合化疗具有抑制端粒酶活性的作用,顺铂+紫杉醇化疗后端粒酶活性下调明显,但未能提高患者5年生存率,可能与化疗药物的耐药性有关。

关键词: 卵巢肿瘤, 端粒酶, hTERT, 化疗, 顺铂

Abstract: Objective To examine possible associations between telomerase activity and clinicopathological features of ovarian epithelial cancer patients and examine the ability of different cisplatin-based chemotherapy protocols to inhibit telomerase activity. Methods Tumor reduction surgery combined with lymph node dissection were performed in 43 patients with primary ovarian epithelial cancer.Cancer tissue from all patients was analyzed by TRAP-PCR-augmentation to detect telomerase activity,RT-PCR to measure hTERT gene expression, and immunohistochemistry to measure hTERT protein expression. Patients were divided into three treatment groups,each of which received an average of 6.5 cycles(range,6-8)of a different cisplatin-based chemotherapy:CC,cisplatin+cyclophosphamide;CP,cisplatin+paclitaxel;CCD,cisplatin+cyclophosphamide+doxorubicin.All patients were subjected to clinical and imaging exams;second-look laparotomy was also performed in patients with normal CA125 levels and no residual tumor(13 CC patients,11 CP patients,and 6 CCD patients).Tissues around the original lesions were checked by biopsy.All patients were followed up to calculate 5-year survival rate. Results Telomerase activity did not correlate with pathology type,grade or FIGO stage in the entire group of patients(P<0.05).All three chemotherapy protocols significantly reduced telomerase activity and hTERT protein expression (P<0.05).The 5-year survival rate was similar for all three protocols(P>0.05). Conclusions Cisplatin-based chemotherapy significantly suppresses telomerase activity.CP chemotherapy can decrease telomerase activity more than CC or CCD therapy, but this does not translate into a higher 5-year survival rate, perhaps because of drug resistance.

Key words:  Ovarian neoplasms, Telomerase, hTERT, Chemotherapy, Cisplatin