MCPH1在宫颈癌中的作用及其靶位治疗的研究

项目名称： MCPH1在宫颈癌中的作用及其靶位治疗的研究

项目编号： No.30800410

项目类型： 青年科学基金项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 袁成福

作者单位： 重庆医科大学

项目金额： 20万元

中文摘要： 宫颈癌是严重危害妇女健康的恶性肿瘤之一，其死亡率高。传统的治疗方法使患者的生存率并不理想。因此探索新的可能的诊断与治疗方法具有重要意义。MCPH1是DNA 检查点反应的重要参与者及调节者，我们推测MCPH1可能在宫颈癌中具有一定作用。我们对宫颈癌标本的Real time PCR检测发现：在31例宫颈癌标本中，癌组织与对应正常宫颈组织比较：12例癌组织中MCPH1 mRNA的表达比正常宫颈组织低；癌组织与对应癌旁组织比较：11例癌组织中MCPH1 mRNA的表达比癌旁组织低。免疫组织化学检查发现在63例标本中有43例（68.3％）宫颈癌组织中MCPH1蛋白的表达低于对应的正常宫颈组织。在体外我们用RNA干扰的方法使 HeLa、SiHa及CaSki细胞中MCPH1 knockdown后，我们并未观察到宫颈癌细胞生长、细胞周期及凋亡的变化；我们将MCPH1 knockdown的CaSki细胞接种裸鼠体内，也并未观察到裸鼠体内肿瘤生长的显著性变化。然而，MCPH1 overexpression却能诱导HeLa、SiHa及CaSki细胞凋亡,这为MCPH1应用于宫颈癌的治疗提供了一定的实验依据。

中文关键词： 宫颈癌；MCPH1基因；RNA干扰；过表达; 凋亡

英文摘要： Cervical cancer is one of the most common cancers in women,the mortality is high.The survival rate is not ideal for the traditional therapeutic methods.Therefore, novel methods for early diagnosis and efficient therapy are still needed for cervical cancer.MCPH1 is an important regulator in DNA checkpoint response. We guess MCPH1 may have some roles in cervical cancer.Quantitative real-time PCR showed that MCPH1 mRNA levels were decreased in 12 of 31 cervical cancer tissue specimens compared with the normal cervical tissue specimens.By immunohistochemistry (IHC),we found MCPH1 protein levels were decreased in 43 of 63(68.3%) cervical cancer tissue specimens compared with the normal cervical tissue specimens. We found MCPH1 knockdown could not affect the cell growth, cell cycle and apoptosis in HeLa, SiHa and CaSki. We also found MCPH1 knockdown could not affect the tumorigenicity of CaSki in nude mice. However, MCPH1 overexpression could induce the apoptosis in HeLa,SiHa and CaSki, this provided the experimental evidence for cervical cancer therapy using MCPH1 overexpression.

英文关键词： cervical cancer; MCPH1 gene; RNA interference; overexpression; apoptosis