Studies have shown that Annexin A2 (ANXA2) is related with tumor proliferation, apoptosis, differentiation, invasion, migration, and drug resistance. The purpose of this study was to investigate the role and its mechanisms of ANXA2 in multidrug-resistance (MDR) in gastric cancer. ANXA2 expression in both gastric cancer tissues and cell lines were detected by quantitative real-time PCR (RT-qPCR) and Western blotting. The cell proliferation was measured by SRB assay. The pool of siRNA against ANXA2 was designed and synthesized and then transfected into resistant gastric cancer SGC7901/DDP cells. ANXA2 expression was detected by RT-qPCR and Western blotting. Drug sensitivities of SGC7901/DDP cells to P-gp-related drug (doxorubicin) and P-gp-non-related drugs (5-FU and cisplatin) were measured by SRB assay. Expression of MDR-related genes and phosphorylation of AKT and MAPKs were also detected by RT-qPCR and Western blotting. Results showed that ANXA2 expression was significantly higher in gastric specimens than that in normal tissues, and negatively correlated with the differentiation level of gastric cancer. In addition, ANXA2 expression level was higher in SGC7901/DDP cells than that in parent 5GC7901 cells. After knock-down ANXA2 expression using ANXA2 small interfering RNA, the drug sensitivity of SGC7901/DDP cells to doxorubicin, 5-FU and DDP increased. Delivery of ANXA2 siRNA significantly downregulated the expression of P-gp, MRP1 and Bcl-2, while markedly upregulated Box in SGC7901/DDP cells. However, several other MDR factors such as GST-pi, TOPO-I and TOPO-II had no obvious changes. Additionally, phosphorylation of P38MAPK and AKT, but not ERK1/2 or JNKs was specifically decreased in SGC7901/DDP cells after ANXA2 siRNA delivery. Importantly, P38MAPK and AKT inhibitor increased the drug sensitivity of SGC701/DDP cells in a similar way as ANXA2 siRNAs does. ANXA2 is involved in gastric cancer MDR through regulating p38MAPK and AKT pathways as well as certain MDR factors.
基金:
Acknowledgments: This work was supported by grants from the
National Natural Science Foundations of China ((No.81072033 to
Yong Li; No. 81372580 to Yong Li) and Hebei Natural Science Foundation
of China (No. C2010000619 to Yong Li); Extra Characteristic
Foundation of Colleges and Universities in Hebei Province (NO.
[2005]52, to Yong Li)
第一作者机构:[1]Department of General Surgery, the Fourth Affiliated Hospital, Hebei Medical University, 12 Jian-Kang St., 050011 Shijiazhuang, China
通讯作者:
通讯机构:[1]Department of General Surgery, the Fourth Affiliated Hospital, Hebei Medical University, 12 Jian-Kang St., 050011 Shijiazhuang, China
推荐引用方式(GB/T 7714):
Zhang Z. D.,Li Y.,Fan L. Q.,et al.Annexin A2 is implicated in multi-drug-resistance in gastric cancer through p38MAPK and AKT pathway[J].NEOPLASMA.2014,61(6):627-637.doi:10.4149/neo_2014_078.
APA:
Zhang, Z. D.,Li, Y.,Fan, L. Q.,Zhao, Q.,Tan, B. B.&Zhao, X. F..(2014).Annexin A2 is implicated in multi-drug-resistance in gastric cancer through p38MAPK and AKT pathway.NEOPLASMA,61,(6)
MLA:
Zhang, Z. D.,et al."Annexin A2 is implicated in multi-drug-resistance in gastric cancer through p38MAPK and AKT pathway".NEOPLASMA 61..6(2014):627-637