限制蛋氨酸可抑制胰腺癌的增殖，同时抑制 JAK2/STAT3 通路。

IF 2.8 2区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Pancreatology Pub Date : 2025-02-01 DOI:10.1016/j.pan.2024.11.023

Manabu Maebashi , Kentaro Miyake , Jun Yamamoto , Kota Sahara , Tomoko Akiyama , Yayoi Kimura , Itaru Endo

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引用次数: 0

摘要

背景：蛋氨酸限制（MR）已被证明在包括胰腺癌（PC）在内的各种类型的癌症中具有抗肿瘤作用。然而，MR诱发的具体机制尚不清楚。本研究旨在通过蛋白质组学分析揭示MR对PC的潜在作用机制。材料与方法：分别在标准培养基和MR培养基中培养人PC细胞株，评价MR的作用，通过蛋白质组学分析评价蛋白表达差异。匠心途径分析（Ingenuity Pathway Analysis， IPA）用于鉴定可能与体外肿瘤生长相关的蛋白质。通过western blotting、real-time PCR和ELISA验证与抗肿瘤作用相关的蛋白。建立皮下PC小鼠的实验模型，通过免疫组织化学染色评估MR饮食的有效性和靶蛋白的表达。结果：与标准培养基相比，MR培养基中细胞增殖受到抑制。IPA分析显示MR组胰腺癌细胞株凋亡通路中STAT3表达减少。Western blotting显示MR降低STAT3表达。Real-time PCR显示MR降低了Panc-1和Mia-PaCa - 2中JAK2和STAT3 mRNA的表达，而在Capan-1中没有。ELISA结果显示MR组NF-kB表达降低。在体内研究中，MR组的最终估计肿瘤体积明显低于对照组(p)。结论：MR抑制了部分PC细胞系的JAK2/STAT3通路，降低了NF-kB。

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Methionine restriction inhibits pancreatic cancer proliferation while suppressing JAK2/STAT3 pathway

Background

Methionine restriction (MR) has been demonstrated to exhibit anti-tumor effects in various types of cancer, including pancreatic cancer (PC). However, the detailed mechanism induced by MR remains still unclear. This study aims to reveal the underlying mechanism of MR on PC by proteomic analysis.

Material & methods

Human PC cell lines were cultured in both standard and MR media to evaluate the effect of MR. The differences in protein expression were evaluated through proteomic analysis. Ingenuity Pathway Analysis (IPA) was performed to identify proteins potentially associated with tumor growth in vitro. The proteins associated with the anti-tumor effect were validated using western blotting, real-time PCR, and ELISA. An experimental model involving subcutaneous PC mice was established for the assessment of the effectiveness of the MR diet and the expression of target proteins through immunohistochemical staining.

Results

Cell proliferation was suppressed in the MR media compared to the standard media. IPA analysis showed that STAT3 was decreased in the Apoptotic Pathway of Pancreatic Cancer Cell lines in the MR group. Western blotting showed MR decreased STAT3 expression. Real-time PCR showed that MR decreased JAK2 and STAT3 mRNA expression in Panc-1 and Mia-PaCa 2, but not in Capan-1. ELISA revealed that NF-kB expression was decreased in the MR group. In the in vivo study, the final estimated tumor volume in the MR group was significantly lower than the control group (p < 0.01). Immunostaining of resected specimens showed that STAT3 expression was suppressed in the MR group.

Conclusion

MR suppressed the JAK2/STAT3 pathway and decreased NF-kB in some PC cell lines.

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来源期刊

Pancreatology 医学-胃肠肝病学

CiteScore

7.20

自引率

5.60%

发文量

194

审稿时长

44 days

期刊介绍： Pancreatology is the official journal of the International Association of Pancreatology (IAP), the European Pancreatic Club (EPC) and several national societies and study groups around the world. Dedicated to the understanding and treatment of exocrine as well as endocrine pancreatic disease, this multidisciplinary periodical publishes original basic, translational and clinical pancreatic research from a range of fields including gastroenterology, oncology, surgery, pharmacology, cellular and molecular biology as well as endocrinology, immunology and epidemiology. Readers can expect to gain new insights into pancreatic physiology and into the pathogenesis, diagnosis, therapeutic approaches and prognosis of pancreatic diseases. The journal features original articles, case reports, consensus guidelines and topical, cutting edge reviews, thus representing a source of valuable, novel information for clinical and basic researchers alike.