Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, China.
Biosci Rep. 2020 Mar 27;40(3). doi: 10.1042/BSR20194142.
Pancreatic cancer (PaCa) is a common malignant tumor of the digestive system with poor prognosis and no ideal treatment for inoperable patients, which is partly due to delayed diagnoses. It is recently reported that the protein histidine phosphatase LHPP is a tumor suppressor in hepatocellular carcinoma, cervical cancer, and bladder cancer. So far, there is no study on the expression level of LHPP in PaCa, and its mechanism of action on tumors is unclear. In this experiment, LHPP expression was lower in cancer tissues than that in normal pancreatic tissue, and clinicopathological results showed that LHPP expression was correlated with the degree of differentiation and lymphatic metastasis of pancreatic carcinoma. The biological characteristics of LHPP in PaCa cells were examined by the cell counting kit-8 assay, transwell assay, and monoclonal formation test. The inhibitory mechanism of LHPP in PaCa cells was determined using Western blotting and flow cytometry. The results showed that LHPP restrained PaCa cell proliferation, migration, and invasion. Increased LHPP expression promoted the apoptosis of PaCa cells through higher activation of cleaved-PARP and cleaved-Casp3 and lower activation of cIAP1. Importantly, the increase in LHPP enhanced PTEN expression and decreased the phosphorylated AKT level. Moreover, LHPP-induced apoptosis was diminished by SC79 (AKT activator) in PaCa cells. In conclusion, LHPP blocks proliferation, migration, and invasion and enhances apoptosis in PaCa cells through the PTEN/AKT signaling pathway.
胰腺癌（PaCa）是一种常见的消化系统恶性肿瘤，预后不良，对于无法手术的患者尚无理想的治疗方法，部分原因是诊断延迟。最近有报道称，组氨酸磷酸酶 LHPP 是肝癌、宫颈癌和膀胱癌的肿瘤抑制因子。迄今为止，尚无关于 LHPP 在 PaCa 中表达水平的研究，其对肿瘤的作用机制尚不清楚。在本实验中，与正常胰腺组织相比，癌组织中 LHPP 的表达水平较低，临床病理结果表明 LHPP 的表达与胰腺癌的分化程度和淋巴转移相关。通过细胞计数试剂盒-8 检测、Transwell 检测和单克隆形成试验研究了 LHPP 在 PaCa 细胞中的生物学特性。通过 Western blot 和流式细胞术确定了 LHPP 在 PaCa 细胞中的抑制机制。结果表明，LHPP 抑制 PaCa 细胞的增殖、迁移和侵袭。通过提高 cleaved-PARP 和 cleaved-Casp3 的活性和降低 cIAP1 的活性，增加 LHPP 表达可促进 PaCa 细胞的凋亡。重要的是，LHPP 增加了 PTEN 的表达并降低了磷酸化 AKT 的水平。此外，在 PaCa 细胞中，SC79（AKT 激活剂）减弱了 LHPP 诱导的细胞凋亡。总之，LHPP 通过 PTEN/AKT 信号通路抑制 PaCa 细胞的增殖、迁移和侵袭，并增强其凋亡。
