LHPP抑制PDAC细胞的活力、迁移和增殖，显著影响SDC1和S100p的表达

2023年1月，中国山东第一医科大学附属医院肝胆外科 (Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China)研究团队在《Technology in Cancer Research & Treatment》上发表论文：

“LHPP Inhibits the Viability, Migration, and Proliferation of PDAC Cells and Significantly Affects the Expression of SDC1 and S100p"

“LHPP抑制PDAC细胞的活力、迁移和增殖，显著影响SDC1和S100p的表达"

Abstract：

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a poor response to chemotherapy and an extremely poor prognosis. Recent studies have revealed that phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) can inhibit the growth of various cancers. Therefore, the current study was conducted to investigate the antitumor effects of LHPP in PDAC and to explore its mechanism using proteomics analysis.

Methods and results: Immunohistochemical analysis of clinical samples demonstrated that LHPP expression levels were lower in tumor tissues compared to adjacent nontumor tissues. Moreover, mu ltivariate COX regression analysis showed that LHPP expression level was an independent prognostic factor for the patients with PDAC. Patients with high LHPP expression had a better prognosis. The lentiviral vectors for normal control (NC), LHPP knockdown (KD), and LHPP overexpression (OE) were infected with BxPC-3 and PANC-1 cell lines. Cell counting kit-8 assay, Transwell assay, and flow cytometry analyses showed that LHPP overexpression significantly inhibited the cell viability, migration, and proliferation of BxPC-3 and PANC-1 cells. Moreover, xenograft tumor model demonstrated that LHPP overexpression inhibited xenograft tumor growth in vivo. Subsequently, proteins with significantly altered expression in BxPC-3 cells after lentivirus infection were detected using proteomics analyses. Interestingly, compared to the NC group, the expression of Syndecan 1 (SDC1) was significantly upregulated in the KD group, while that of S100P was significantly downregulated in the OE group.

Conclusion: LHPP might emerge as an important target for delaying the advancement of PDAC, thereby providing a novel therapeutic approach for the treatment of PDAC.

摘要：

胰腺导管腺癌(Pancreatic ductal adencarcinoma, PDAC)是一种高度侵袭性的恶性肿瘤，对化疗反应差，预后极差。近年来的研究表明，磷酸赖氨酸磷组氨酸无机焦磷酸盐磷酸酶(LHPP)可以抑制多种癌症的生长。因此，本研究通过蛋白质组学分析，探讨LHPP在PDAC中的抗肿瘤作用，并探讨其作用机制。

方法和结果:临床样本免疫组化分析显示，肿瘤组织中LHPP表达水平低于邻近非肿瘤组织。多因素COX回归分析显示LHPP表达水平是影响PDAC患者预后的独立因素。LHPP高表达患者预后较好。用BxPC-3和PANC-1细胞株感染正常对照(NC)、LHPP敲低(KD)和LHPP过表达(OE)慢病毒载体。细胞计数试剂盒-8、Transwell实验和流式细胞术分析显示，LHPP过表达显著抑制BxPC-3和PANC-1细胞的活力、迁移和增殖。此外，异种移植瘤模型表明，LHPP过表达抑制异种移植瘤的体内生长。随后，利用蛋白质组学分析检测慢病毒感染后BxPC-3细胞中表达显著改变的蛋白。有趣的是，与NC组相比，KD组Syndecan 1 (SDC1)的表达显著上调，OE组S100P的表达显著下调。

结论:LHPP可能成为延缓PDAC进展的重要靶点，为PDAC的治疗提供了一种新的治疗途径。

该论文中，人胰腺导管腺癌细胞系(BxPC-3和PANC-1)体外培养是使用Ausbian特级胎牛血清完成的。