Kallikrein-related peptidase 7 is a potential target for the treatment of pancreatic cancer.
Kallikrein-related peptidase 7 is a potential target for the treatment of pancreatic cancer.
复制标题
激肽释放酶相关肽酶 7 是治疗胰腺癌的潜在靶点。
DOI：
10.18632/oncotarget.24132
复制
发表时间：
2018-02-27
期刊：
影响因子：
--
通讯作者：
Tan X
中科院分区：
文献类型：
--
作者：
Du JP;Li L;Zheng J;Zhang D;Liu W;Zheng WH;Li XS;Yao RC;Wang F;Liu S;Tan X
胰腺癌是最致命的癌症之一，预后极差，患者确诊后的五年生存率不到5%。激肽释放酶相关肽酶（KLK）属于丝氨酸蛋白酶家族，有15个成员，在细胞生理行为和疾病中发挥重要作用。KLK 7在胰腺癌组织中的高表达水平被认为是胰腺癌预后不良的标志。在这项工作中，我们着手研究KLK 7是否可以成为胰腺癌治疗的靶点。设计并构建短发夹状RNA（shorthairpin RNA，shRNAs），在慢病毒载体中敲除胰腺癌细胞株PANC-1中的KLK 7，并采用真实的时间细胞分析（real time cellular analysis，RTCA）方法检测细胞的增殖、迁移和侵袭能力。通过计算机辅助药物筛选发现了抑制KLK 7的小分子，并用于抑制PANC-1细胞。我们的结果证实KLK 7在胰腺癌组织中显著上调，敲低或抑制KLK 7可有效抑制胰腺癌细胞的增殖、迁移和侵袭。本研究提示KLK 7可能成为胰腺癌潜在的化疗靶点，为胰腺癌的治疗提供了新的策略。
Pancreatic cancer is one of the deadliest cancers with very poor prognosis, and the five-year survival rate of the patients is less than 5% after diagnosis. Kallikrein-related peptidases (KLKs) belong to a serine protease family with 15 members that play important roles in cellular physiological behavior and diseases. The high expression level of KLK7 in pancreatic cancer tissues is considered to be a marker for the poor prognosis of this disease. In this work, we set out to investigate whether KLK7 could be a target for the treatment of pancreatic cancer. Short hairpin RNAs (shRNAs) were designed and constructed in lentivirus to knock down KLK7 in pancreatic cancer cell line PANC-1, and the real time cellular analysis (RTCA) was used to evaluate cell proliferation, migration and invasion abilities. Small molecules inhibiting KLK7 were discovered by computer-aided drug screening and used to inhibit PANC-1 cells. Our results confirmed that KLK7 is significantly up-regulated in pancreatic cancer tissue, and knocking down or inhibiting KLK7 efficiently inhibited the proliferation, migration and invasion of pancreatic cancer cells. This study suggested that KLK7 could be a potential chemotherapy target for treatment of pancreatic cancer, which would provide us a novel strategy for the treatment of this disease.