CAPZA1在人胰腺癌侵袭转移中的作用及机制

The role and mechanism of capping actin protein of muscle Z - line alpha subunit 1 in invasion andmetastasis of human pancreatic cancer

目的观察CAPZA1在胰腺癌组织中的表达及与预后的关系，探讨CAPZA1调控胰腺细胞的侵袭转移的作用及机制。 方法采用免疫组织化学法检测CAPZA1和上皮-间充质转化（EMT）标志物在胰腺癌组织中的表达，统计分析胰腺癌患者的预后情况。Western blot、实时定量反转录聚合酶链反应（RT-qPCR）检测胰腺癌细胞中CAPZA1和EMT标志物的表达。Transwell、细胞计数试剂盒（CCK-8）检测胰腺癌细胞的迁移、侵袭和增殖。 结果CAPZA1表达水平与胰腺癌的生物学特性及患者的预后呈负相关。CAPZA1的表达水平与胰腺癌的侵袭转移潜能呈负相关，抑制CAPZA1的表达可促进胰腺癌的侵袭转移（192.0±13.8比153.0±17.1，P＝0.004），而过表达CAPZA1可抑制胰腺癌的侵袭转移（107.0±18.5比153.0±17.1，P＝0.004）。过表达CAPZA1可以上调EMT标志物E-钙黏蛋白（E-cadherin，0.76±0.09比0.57±0.14，P＝0.034）而抑制N-钙黏蛋白（N-cadherin，0.53±0.12比0.74±0.10，P＝0.017）和波形蛋白（Vimentin，0.56±0.20比0.93±0.19，P＝0.017）的表达。 结论CAPZA1可通过调控肌动蛋白骨架的装配，从而抑制胰腺癌细胞EMT，降低胰腺癌细胞的侵袭能力。

ObjectiveTo observe the expression of capping actin protein of muscle Z-line alpha subunit 1 （CAPZA1） in pancreatic cancer and its relationship with prognosis, and explore the role and mechanism of CAPZA1 in regulating the invasion and metastasis of pancreatic cancer cells. MethodsImmunohistochemistry was used to detect the expression of CAPZA1 and epithelial-mesenchymal transition （EMT） markers in pancreatic cancer tissues. The statistical analysis was made on the prognosis of patients with pancreatic cancer. Western blotting and real-time reverse transcriptase-polymerase chain reaction （RT-qPCR） were used to detect the expression of CAPZA1 and EMT markers in pancreatic cancer cells. Transwell, and cell counting kit-8 （CCK-8） were used to detect migration, invasion and proliferation of pancreatic cancer cells. ResultsThe expression of CAPZA1 was negatively correlated with the biological characteristics of pancreatic cancer cells and the prognosis of patients. The expression of CAPZA1 was negatively correlated with the invasion and metastasis potentials of pancreatic cancer cells. Inhibition of CAPZA1 expression could promote the invasion and metastasis of pancreatic cancer cells （192.0±13.8 vs. 153.0±17.1, P=0.004）, while over-expression of CAPZA1 could inhibit the invasion and metastasis of pancreatic cancer cells （107.0±18.5 vs. 153.0±17.1, P=0.004）. The expression of CAPZA1 was correlated with the expression of EMT markers E-cadherin （0.76±0.09 vs. 0.57±0.14, P=0.034）, N-cadherin （0.53±0.12 vs. 0.74±0.10, P=0.017） and Vimentin （0.56±0.20 vs. 0.93±0.19, P=0.017）. ConclusionCAPZA1 can inhibit the EMT of pancreatic cancer cells and reduce the invasion ability of them0 by regulating the assembly of cell skeleton.