Wu Ying, Meng Li, Wang Hui, Xu Qian, Wang Shixuan, Wu Sufang, Xi Ling, Zhao Yun, Zhou Jianfeng, Xu Gang, Lu Yuping, Ma Ding
Cancer Biology Research Center, Tongji Hospital, Tongji Medical School, Huazhong University of Science and Technology, Hubei 430030, PR China.
Oncol Rep. 2006 Sep;16(3):625-9.
The purpose of this study was to determine the effect of the FHIT gene on tumorigenesis of cervical cancer. RT-PCR and MTT were used to detect the expression of FHIT and cell proliferation respectively. Flow cytometry was used to test cell cycle and cell apoptosis. The expression of FHIT was not induced at all four cervical cancer cells treated with demethylating agent 5-aza-2'-deoxycytidine (5-Aza-CdR). However, a constant level of FHIT expression was detected in the human umbilical vein endothelial cell before and after 5-aza-dC treatment. The proliferation of all four cervical cancer cells was inhibited evidently when treated with 5-aza-dC and the inhibiting rate of cell growth along with the increasing concentration of 5-aza-dC. There was no obvious inhibiting effect on the growth of the human umbilical vein endothelial cell treated with 5-aza-dC. An increasing G1 phase and high apoptosis rate were detected in all four cervical cancer cells. However, a negligible change was seen in the human umbilical vein endothelial cell. These results suggest that aberrant methylation of the FHIT gene might be a key mechanism for silenced FHIT gene, which could be reactivated and whose tumor suppressing function could be restored by demethylating agent treatment.
本研究的目的是确定FHIT基因对宫颈癌肿瘤发生的影响。分别采用逆转录聚合酶链反应（RT-PCR）和噻唑蓝比色法（MTT）检测FHIT的表达和细胞增殖情况。采用流式细胞术检测细胞周期和细胞凋亡情况。用去甲基化剂5-氮杂-2'-脱氧胞苷（5-Aza-CdR）处理的4种宫颈癌细胞均未诱导出FHIT的表达。然而，在5-氮杂-2'-脱氧胞苷（5-aza-dC）处理前后的人脐静脉内皮细胞中均检测到稳定水平的FHIT表达。用5-aza-dC处理时，4种宫颈癌细胞的增殖均明显受到抑制，且细胞生长抑制率随5-aza-dC浓度的增加而升高。5-aza-dC对人脐静脉内皮细胞的生长没有明显的抑制作用。在4种宫颈癌细胞中均检测到G1期增加和高凋亡率。然而，人脐静脉内皮细胞中未见明显变化。这些结果表明，FHIT基因的异常甲基化可能是FHIT基因沉默的关键机制，去甲基化剂处理可使其重新激活并恢复其肿瘤抑制功能。
