B7-H3 combats apoptosis induced by chemotherapy by delivering signals to pancreatic cancer cells.
B7-H3 combats apoptosis induced by chemotherapy by delivering signals to pancreatic cancer cells.
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DOI：
10.18632/oncotarget.20421
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发表时间：
2017-09-26
期刊：
影响因子：
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通讯作者：
Zhao X
中科院分区：
文献类型：
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作者：
Li D;Wang J;Zhou J;Zhan S;Huang Y;Wang F;Zhang Z;Zhu D;Zhao H;Li D;Chen G;Zhu X;Zhao X
本研究旨在探讨B7-H3在胰腺癌细胞化疗耐药中的作用，发现其潜在的信号转导途径和分子靶点。免疫组织化学染色和实时定量聚合酶链式反应(RT-PCR)检测临床标本中B7-H3的表达。临床资料用于生存分析。用磷酸化蛋白纯化试剂盒从培养的Patu8988细胞中纯化出磷酸化蛋白。用碘化丙啶-膜联蛋白V染色检测细胞凋亡，探讨吉西他滨对Patu8988细胞B7-H3表达的影响。用免疫印迹法检测B7-H3对细胞外信号调节激酶1/2、表皮生长因子受体和核因子κB抑制因子(I-κB)等蛋白表达的影响。B7-H3在胰腺癌组织中的表达高于正常组织。生存分析显示，B7-H3低表达组的患者总生存期可能比高表达组的患者长(P<；0.05)。经4H7激活的B7-H3可减少吉西他滨诱导的Patu8988细胞的凋亡。4H7激活B7-H3可引起p-ERK1/2、表皮生长因子受体和IκB蛋白水平的变化。当B7-H3表达上调时，EGFR和p-ERK1/2蛋白的表达水平显著升高(P<；0.05)，而I-κB的表达水平显著降低(P<；0.05)，尤以吉西他滨组最为明显。本研究证明B7-H3可以向胰腺癌细胞传递信号以对抗吉西他滨诱导的细胞凋亡。
This study aimed to investigate the role of B7-H3 in chemotherapy resistance of pancreatic cancer cells and discover the potential signal transduction pathway and molecular targets involved. Immunohistochemical staining and real-time polymerase chain reaction (PCR) were used to determine the expression of B7-H3 in clinical specimens. Clinical data were applied to survival analysis. Phosphoprotein was purified from cultured Patu8988 cells using the Phosphoprotein Purification Kit. Cell apoptosis was detected using propidium iodide–Annexin V staining to investigate the relation between the expression of B7-H3 and Patu8988 cells treated with gemcitabine. Western blot was used to determine the effect of B7-H3 on the expression of proteins including extracellular signal–regulated kinase (ERK)1/2, epidermal growth factor receptor (EGFR), and Inhibitor of NF-κB(IκB) in Patu8988 cells; B7-H3 was activated by 4H7, which as an agonist monoclonal antibody to B7-H3. The expression of B7-H3 was found to be higher in tumor tissues than in normal tissues of pancreatic carcinoma. Survival analysis revealed that patients in the low-B7-H3 expression group were likely to have a longer overall survival compared with those in the high-expression group (P < 0.05). B7-H3 activated by 4H7 could reduce gemcitabine-induced apoptosis in Patu8988 cells. Activation of B7-H3 by 4H7 induced variations in p-ERK1/2, EGFR, and IκB protein levels. When B7-H3 was upregulated, the expression levels of EGFR and p-ERK1/2 proteins significantly increased (P < 0.05), but the expression level of IκB significantly decreased (P < 0.05), especially in the gemcitabine-treated group. This study demonstrated that B7-H3 could deliver signals to pancreatic cancer cells to combat apoptosis induced by gemcitabine.