Bmi-1 Promotes the Chemoresistance, Invasion and Tumorigenesis of Pancreatic Cancer Cells
Bmi-1 Promotes the Chemoresistance, Invasion and Tumorigenesis of Pancreatic Cancer Cells
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DOI：
10.1159/000334103
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发表时间：
2012-01
期刊：
影响因子：
3.3
通讯作者：
T. Yin;Hongji Wei;Z. Leng;Zhiyong Yang;S. Gou;Heshui Wu;Gang Zhao;Xiaoqing Hu;Chun-you Wang
中科院分区：
文献类型：
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作者：
T. Yin;Hongji Wei;Z. Leng;Zhiyong Yang;S. Gou;Heshui Wu;Gang Zhao;Xiaoqing Hu;Chun-you Wang
背景/目的：多梳蛋白Bmi-1在多种癌症中起致瘤作用。本研究旨在探讨Bmi-1在胰腺癌化疗耐药、侵袭和肿瘤发生等恶性行为中的作用。方法与结果：MTT细胞增殖实验显示shRNA介导的Bmi-1敲低增强了胰腺癌细胞对吉西他滨的化疗敏感性。transwell侵袭实验表明，敲低Bmi-1抑制胰腺癌细胞的体外侵袭。值得注意的是，化疗耐药和侵袭能力的降低与胰腺癌细胞从间充质表型向上皮表型的转变有关。此外，Bmi-1敲低导致PI3K-Akt通路的抑制，破坏了胰腺癌细胞的球形形成能力。裸鼠异种移植实验表明，缺乏Bmi-1的胰腺癌细胞在体内表现出较弱的致瘤性。结论：我们的数据提示Bmi-1在胰腺癌的进展中起重要作用，是胰腺癌抗肿瘤治疗的新靶点。
Background/Aims: The polycomb protein Bmi-1 plays oncogenic roles in various cancers. Here we aimed to investigate the contribution of Bmi-1 on the malignant behaviors of pancreatic cancer such as chemoresistance, invasion and tumorigenesis. Methods and Results: The MTT cell proliferation assay showed that shRNA mediated Bmi-1 knockdown and enhanced the chemosensitivity of pancreatic cancer cells to gemcitabine. The transwell invasion assay showed that Bmi-1 knockdown inhibited the invasion of pancreatic cancer cells in vitro. Notably, the reduced abilities of chemoresistance and invasion were associated with the transition from the mesenchymal phenotype to the epithelial phenotype of pancreatic cancer cells. Moreover, Bmi-1 knockdown led to the inhibition of the PI3K-Akt pathway and disrupted the sphere-forming abilities of pancreatic cancer cells. A nude mouse xenograft experiment demonstrated that pancreatic cancer cells depleted of Bmi-1 showed weak tumorigenicity in vivo. Conclusion: Our data suggest that Bmi-1 plays an important role in the progression of pancreatic cancer and represents a novel target for antitumor therapy of pancreatic cancer.