Yao Guo-Wang, Bai Jing-Rui, Zhang Da-Peng
Department of the 1st Hepato-Biliary-Pancreatic Surgery, Tianjin Nankai Hospital, Tianjin 300100, P.R. China.
Oncol Lett. 2019 Apr;17(4):3709-3718. doi: 10.3892/ol.2019.10040. Epub 2019 Feb 14.
Pancreatic cancer has an overall 5-year survival rate of only 9%, due to its rapid metastasis and poor prognosis. To combat this disease, novel therapeutic targets and biomarkers are required. In this study, immunohistochemistry was used to detect the expression of P21 activated kinase 2 (PAK2) protein in the tissues of cancer and the paired adjacent normal tissues. The association between PAK2 and the clinicopathologic features of patients with pancreatic cancer was subsequently analyzed. The results indicated that PAK2 was overexpressed in the cancer tissues, which indicated high pTNM stage, poor tumor grade, lymph node metastasis and vascular invasion. In addition, the results demonstrated evidence of a close association between PAK2 expression and poor prognosis of patients with pancreatic cancer. The results also suggested that PAK2 may promote pancreatic cancer cell proliferation and migration through clone formation, MTT, wound healing and Transwell assays. The present study further identified that PAK2 could stimulate pancreatic cancer growth and metastasis in mice. Decreased expression of proliferation marker protein Ki-67 and proliferating cell nuclear antigen in response to PAK2 knockdown further verified the role of PAK2 in promoting cell proliferation by western blot analysis. In addition, the expression levels of matrix metallopeptidase (MMP) 2 and MMP9 were decreased in PANC1 and BxPC3 cell lines transfected with PAK2-short hairpin RNA as indicated in western blot analysis, suggesting a function of PAK2 in promoting cell invasion. Collectively, these findings revealed a critical role for PAK2 in the development of pancreatic cancer and may have important implications for the management of this disease.
胰腺癌的总体5年生存率仅为9%，这是由于其快速转移和预后不良所致。为了对抗这种疾病，需要新的治疗靶点和生物标志物。在本研究中，采用免疫组织化学法检测胰腺癌组织及配对的癌旁正常组织中P21激活激酶2（PAK2）蛋白的表达。随后分析PAK2与胰腺癌患者临床病理特征之间的关联。结果表明，PAK2在癌组织中高表达，提示pTNM分期高、肿瘤分级差、有淋巴结转移和血管侵犯。此外，结果表明PAK2表达与胰腺癌患者预后不良密切相关。结果还提示，PAK2可能通过克隆形成、MTT、伤口愈合和Transwell实验促进胰腺癌细胞增殖和迁移。本研究进一步证实，PAK2可促进小鼠胰腺癌的生长和转移。通过蛋白质免疫印迹分析，PAK2敲低后增殖标志物蛋白Ki-67和增殖细胞核抗原表达降低，进一步证实了PAK2在促进细胞增殖中的作用。此外，蛋白质免疫印迹分析表明，在转染PAK2短发夹RNA的PANC1和BxPC3细胞系中，基质金属蛋白酶（MMP）2和MMP9的表达水平降低，提示PAK2在促进细胞侵袭中发挥作用。总的来说，这些发现揭示了PAK2在胰腺癌发生发展中的关键作用，可能对该疾病的治疗具有重要意义。
