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[多梳蛋白Bmi1靶向治疗结直肠癌的机制]

[Mechanism of polycomb Bmi1-targeted therapy for colorectal cancer].

作者信息

Zhang Hui, Ye Ying-jiang, Cui Zhi-rong, Wang Shan

机构信息

Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, China.

出版信息

Zhonghua Wei Chang Wai Ke Za Zhi. 2011 Aug;14(8):623-6.

PMID:21866458
Abstract

OBJECTIVE

To investigate the Bmi1 protein level in human colorectal cancer specimen and associated clinicopathological parameters, and to determine the influence of Bmi1 on the proliferation and apoptosis of colorectal cancer cells.

METHODS

Bmi1 protein level was assessed in 85 patients with colorectal cancer and adjacent normal tissue by immunohistochemistry. SW480 cells were transfected with Bmi siRNA plasmid. MTT assay and flow cytometry were used to measure the proliferation and apoptosis of SW480 cells. The expression of Bmi1 and Bcl-2 were measured by Western blot.

RESULTS

The positive rate of Bmi1 expression in colorectal cancer tissues was 56.5%(48/85), significantly higher than that in the adjacent noncancerous tissues[17.6%(15/85), P<0.05)]. It was found that the overexpression of Bmi1 was associated with degree of differentiation, status of lymph nodes metastasis, and TNM staging in colorectal cancer(P<0.05). After transfection of SW480 with Bmi1 siRNA, the cell proliferation was inhibited and the apoptosis was significant. The cell proliferation inhibitory rates were 13.1%, 16.5%, and 18.3% at 24 h, 48 h and 72 h after transfection. The apoptotic rates were 15.7%, 45.6%, 40.2%, respectively. Expression of Bmi1 was downregulated after 48 h, as was that of Bcl-2.

CONCLUSIONS

Bmi1 expression is associated with the clinicopathological characteristics of colorectal cancer. Blockade of Bmi1 can inhibit the proliferation and accelerate the apoptosis of colorectal cancer cells.

摘要

目的

探讨人结直肠癌标本中Bmi1蛋白水平及其与临床病理参数的关系,并确定Bmi1对结直肠癌细胞增殖和凋亡的影响。

方法

采用免疫组织化学法检测85例结直肠癌患者及其癌旁正常组织中Bmi1蛋白水平。将Bmi siRNA质粒转染SW480细胞。采用MTT法和流式细胞术检测SW480细胞的增殖和凋亡情况。采用蛋白质免疫印迹法检测Bmi1和Bcl-2的表达。

结果

结直肠癌组织中Bmi1表达阳性率为56.5%(48/85),显著高于癌旁非癌组织[17.6%(15/85),P<0.05]。发现Bmi1的过表达与结直肠癌的分化程度、淋巴结转移状态及TNM分期相关(P<0.05)。用Bmi1 siRNA转染SW480细胞后,细胞增殖受到抑制,凋亡明显。转染后24 h、48 h和72 h的细胞增殖抑制率分别为13.1%、16.5%和18.3%。凋亡率分别为15.7%、45.6%、40.2%。48 h后Bmi1表达下调,Bcl-2表达也下调。

结论

Bmi1表达与结直肠癌的临床病理特征相关。阻断Bmi1可抑制结直肠癌细胞的增殖并加速其凋亡。

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