Annexin A5 inhibits diffuse large B-cell lymphoma cell invasion and chemoresistance through phosphatidylinositol 3-kinase signaling

作者：Wang, Jingjing; Zhang, Yang; Liu, Xianling; Ma, Jinan; Liu, Ping; Hu, Chunhong^*; Zhang, Guangsen

来源：Oncology Reports, 2014, 32(6): 2557-2563.

DOI：10.3892/or.2014.3547

• diffuse large B-cell lymphoma
• Annexin A5
• invasion
• chemoresistance
• CHOP chemotherapy
• phosphatidylinositol 3-kinase

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma worldwide. Although patient outcomes have significantly improved to a greater than 40% cure rate by the combinatorial cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy, which is widely used, resistance to the CHOP regimen continues to pose a problem in managing or curing DLBCL. While it promotes the malignancy and chemoresistance in certain types of cancer, Annexin A5 is negatively correlated with those in other cancers, including DLBCL. In the present study, we explored the effects of Annexin AS on DLBCL cell invasion and chemoresistance to CHOP. Stable overexpression and knockdown of Annexin AS were performed in Toledo and Pfeiffer human DLBCL cell lines. Overexpression of Annexin AS in both cell lines significantly decreased cell invasion, matrix metalloproteinase-9 (MMP-9) expression/activity, phosphatidylinositol 3-kinase (PI3K) activity/Akt phosphorylation, and cell survival against CHOP-induced apoptosis. On the other hand, knockdown of Annexin AS markedly increased cell invasion, MMP-9 expression/activity, PI3K activity/Akt phosphorylation, and CHOP-induced apoptosis in the DLBCL cell lines, which was abolished by selective PI3K inhibitor BKM120. In conclusion, our study provides the first in vitro evidence that Annexin AS inhibits DLBCL cell invasion, MMP-9 expression/activity, and chemoresistance to CHOP through a PI3K-dependent mechanism; it provides new insight not only into the biological function of Annexin A5, but also into the molecular mechanisms underlying DLBCL progression and chemoresistance.

• 出版日期2014-12
• 单位中南大学