Fatty acid metabolism regulated by FATP1 promotes lymph node colonization in cholangiocarcinoma

doi:10.3969/j.issn.1009-976X.2025.02.001

Abstract

Abstract: Objective To investigate the mechanism and therapeutic strategy of fatty acid transport protein 1 （FATP1） on lymph node colonization of cholangiocarcinoma （CCA）. Methods Subcutaneous tumor-bearing mouse models and lymph node orthotopic tumor-bearing mouse models were established. Tumor tissues at different tumor stages were collected, and proteomics was used to screen key proteins in cholangiocarcinoma colonization in lymph nodes. Immunohistochemical staining was used to evaluate the correlation between FATP1 expression in lymph node metastases of cholangiocarcinoma and poor prognosis of patients. CCK-8 cell proliferation assay and Nile red staining were used to detect the changes in lipid metabolism and proliferation ability of cholangiocarcinoma cells （HUCCT1, HCCC9810） before and after knockdown or overexpression of FATP1. In vitro and in vivo experiments were used to verify that FATP1 inhibitor （FATP1-IN-1） inhibited cholangiocarcinoma colonization in lymph nodes by targeting lipid metabolism. Results Proteomic screening results suggested that FATP1 played a key role in the process of cholangiocarcinoma colonization of lymph nodes. Immunohistochemical staining showed that FATP1 was more highly expressed in lymph node metastases and was associated with poor prognosis of patients. In vitro experiments showed that knocking down FATP1 inhibited cholangiocarcinoma proliferation and lipid accumulation, while overexpression of FATP1 enhanced the above phenotypes. FATP1 inhibitor （FATP1-IN-1） significantly inhibited cancer cell proliferation in vitro and reduced tumor burden and lipid accumulation in an in vivo model. Conclusion Fatty acid metabolism regulated by FATP1 promotes cholangiocarcinoma colonization in lymph nodes, and targeting FATP1 can effectively inhibit the progression of lymph node colonized tumors.

Key words: cholangiocarcinoma, lymph node metastasis, metastatic colonization, FATP1, FATP1-IN-1

摘要： 目的探讨脂肪酸转运蛋白1（FATP1）对胆管癌（CCA）定植于淋巴结的机制及治疗策略。方法构建皮下荷瘤小鼠模型和淋巴结原位荷瘤小鼠模型,收集不同成瘤时期的肿瘤组织,蛋白组学筛选胆管癌定植于淋巴结的关键蛋白;通过免疫组化染色评估胆管癌淋巴结转移灶FATP1表达与病人预后不良的相关性。采用CCK-8细胞增殖实验和尼罗红染色等检测敲低或过表达FATP1前后胆管癌细胞（HUCCT1、HCCC9810）脂代谢及增殖能力的变化;并通过体内外实验验证FATP1抑制剂（FATP1-IN-1）通过靶向胆管癌的脂代谢抑制其在淋巴结中的定植。结果蛋白组学筛选结果提示FATP1在胆管癌定植淋巴结的过程中发挥关键作用。免疫组化染色显示,FATP1在淋巴结转移灶表达水平显著上调并且与病人预后不良相关（所有P<0.05）。体外实验表明,敲低FATP1抑制胆管癌增殖及脂质堆积,过表达FATP1则增强上述表型。FATP1抑制剂（FATP1-IN-1）在体外显著抑制癌细胞增殖,并在体内模型中降低肿瘤负荷及脂质积累。结论 FATP1调控的脂肪酸代谢促进胆管癌定植于淋巴结,靶向FATP1可有效抑制淋巴结定植肿瘤的进展。

关键词: 胆管癌, 淋巴结转移, 转移定植, FATP1, FATP1-IN-1

CLC Number:

R735.8

LI Xiu-xian, SONG Zhi-xiao, ZHANG Hong-hua, LIU Chao. Fatty acid metabolism regulated by FATP1 promotes lymph node colonization in cholangiocarcinoma[J]. Lingnan Modern Clinics In Surgery, 2025, 25(02): 75-83.

李修贤, 宋之潇, 张洪华, 刘超. FATP1调控的脂肪酸代谢促进胆管癌淋巴结定植[J]. 岭南现代临床外科, 2025, 25(02): 75-83.

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