LHPP抑制PDAC細(xì)胞的活力、遷移和增殖，顯著影響SDC1和S100p的表達(dá)

2023年1月，中國山東第一醫(yī)科大學(xué)附屬醫(yī)院肝膽外科 (Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China)研究團(tuán)隊(duì)在《Technology in Cancer Research & Treatment》上發(fā)表論文：

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

“LHPP抑制PDAC細(xì)胞的活力、遷移和增殖，顯著影響SDC1和S100p的表達(dá)"

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：

胰腺導(dǎo)管腺癌(Pancreatic ductal adencarcinoma, PDAC)是一種高度侵襲性的惡性腫瘤，對化療反應(yīng)差，預(yù)后極差。近年來的研究表明，磷酸賴氨酸磷組氨酸無機(jī)焦磷酸鹽磷酸酶(LHPP)可以抑制多種癌癥的生長。因此，本研究通過蛋白質(zhì)組學(xué)分析，探討LHPP在PDAC中的抗腫瘤作用，并探討其作用機(jī)制。

方法和結(jié)果:臨床樣本免疫組化分析顯示，腫瘤組織中LHPP表達(dá)水平低于鄰近非腫瘤組織。多因素COX回歸分析顯示LHPP表達(dá)水平是影響PDAC患者預(yù)后的獨(dú)立因素。LHPP高表達(dá)患者預(yù)后較好。用BxPC-3和PANC-1細(xì)胞株感染正常對照(NC)、LHPP敲低(KD)和LHPP過表達(dá)(OE)慢病毒載體。細(xì)胞計(jì)數(shù)試劑盒-8、Transwell實(shí)驗(yàn)和流式細(xì)胞術(shù)分析顯示，LHPP過表達(dá)顯著抑制BxPC-3和PANC-1細(xì)胞的活力、遷移和增殖。此外，異種移植瘤模型表明，LHPP過表達(dá)抑制異種移植瘤的體內(nèi)生長。隨后，利用蛋白質(zhì)組學(xué)分析檢測慢病毒感染后BxPC-3細(xì)胞中表達(dá)顯著改變的蛋白。有趣的是，與NC組相比，KD組Syndecan 1 (SDC1)的表達(dá)顯著上調(diào)，OE組S100P的表達(dá)顯著下調(diào)。

結(jié)論:LHPP可能成為延緩PDAC進(jìn)展的重要靶點(diǎn)，為PDAC的治療提供了一種新的治療途徑。

該論文中，人胰腺導(dǎo)管腺癌細(xì)胞系(BxPC-3和PANC-1)體外培養(yǎng)是使用Ausbian特級胎牛血清完成的。