Pancreatic Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
Chemotherapy. 2011;57(6):488-96. doi: 10.1159/000334103. Epub 2012 Jan 13.
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.
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.
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.
背景/目的：多梳蛋白 Bmi-1 在多种癌症中发挥致癌作用。本研究旨在探讨 Bmi-1 对胰腺癌的恶性行为（如化疗耐药性、侵袭和肿瘤发生）的贡献。
MTT 细胞增殖实验表明，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，Bmi-1 敲低抑制了胰腺癌细胞的体外侵袭。值得注意的是，化疗耐药性和侵袭能力的降低与胰腺癌细胞从中胚层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，并破坏了胰腺癌细胞的球体形成能力。裸鼠异种移植实验表明，Bmi-1 耗尽的胰腺癌细胞在体内的致瘤性较弱。
我们的数据表明，Bmi-1 在胰腺癌的进展中发挥重要作用，代表了胰腺癌抗肿瘤治疗的一个新靶点。
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