Du Jian Ping, Li Lin, Zheng Jun, Zhang Ding, Liu Wei, Zheng Wei Hong, Li Xiao Song, Yao Ru Cheng, Wang Fangyu, Liu Sen, Tan Xiao
Institute of Hepatopancreatobilary Surgery, China Three Gorges University, Yichang 443003, P.R. China.
The First College of Clinical Medical Science, China Three Gorges University, Yichang, 443003, P.R. China.
Oncotarget. 2018 Jan 10;9(16):12894-12906. doi: 10.18632/oncotarget.24132. eCollection 2018 Feb 27.
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.
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（KLKs）属于丝氨酸蛋白酶家族，由15个成员组成，在细胞生理行为和疾病中发挥重要作用。胰腺癌组织中KLK7的高表达水平被认为是该疾病预后不良的一个标志物。在这项研究中，我们着手研究KLK7是否可以成为治疗胰腺癌的靶点。设计并构建了短发夹RNA（shRNAs）慢病毒载体，以敲低胰腺癌细胞系PANC-1中的KLK7，并使用实时细胞分析（RTCA）评估细胞增殖、迁移和侵袭能力。通过计算机辅助药物筛选发现了抑制KLK7的小分子，并用于抑制PANC-1细胞。我们的结果证实，KLK7在胰腺癌组织中显著上调，敲低或抑制KLK7可有效抑制胰腺癌细胞的增殖、迁移和侵袭。本研究表明，KLK7可能是治疗胰腺癌的潜在化疗靶点，这将为我们提供一种治疗该疾病的新策略。
