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一种新型多药耐药细胞系源自一位中国胰腺导管腺癌患者。

A novel multidrug-resistant cell line from a Chinese patient with pancreatic ductal adenocarcinoma.

机构信息

The Second Clinical Medical School of Lanzhou University, Lanzhou, 730000, China.

The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310006, China.

出版信息

Sci Rep. 2024 Apr 22;14(1):9259. doi: 10.1038/s41598-024-56464-w.

Abstract

Chemotherapy resistance poses clinical challenges in pancreatic cancer treatment. Developing cell lines resistant to chemotherapy is crucial for investigating drug resistance mechanisms and identifying alternative treatment pathways. The genetic and biological attributes of pancreatic cancer depend on its aetiology, racial demographics and anatomical origin, underscoring the need for models that comprehensively represent these characteristics. Here, we introduce PDAC-X2, a pancreatic cancer cell line derived from Chinese patients. We conducted a comprehensive analysis encompassing the immune phenotype, biology, genetics, molecular characteristics and tumorigenicity of the cell line. PDAC-X2 cells displayed epithelial morphology and expressed cell markers (CK7 and CK19) alongside other markers (E-cadherin, Vimentin, Ki-67, CEA and CA19-9). The population doubling time averaged around 69 h. In vivo, PDAC-X2 cells consistently maintained their tumorigenicity, achieving a 100% tumour formation rate. Characterised by a predominantly tetraploid karyotype, this cell line exhibited a complex genetic markup. Notably, PDAC-X2 cells demonstrated resistance to multiple drugs, including gemcitabine, paclitaxel, 5-fluorouracil and oxaliplatin. In conclusion, PDAC-X2 presents an invaluable preclinical model. Its utility lies in facilitating the study of drug resistance mechanisms and the exploration of alternative therapeutic approaches aimed at enhancing the prognosis of this tumour type.

摘要

化疗耐药性给胰腺癌的治疗带来了临床挑战。开发对化疗耐药的细胞系对于研究耐药机制和寻找替代治疗途径至关重要。胰腺癌的遗传和生物学特征取决于其病因、种族人口统计学和解剖起源,这强调了需要建立能够全面代表这些特征的模型。在这里,我们引入了 PDAC-X2,这是一种源自中国患者的胰腺癌细胞系。我们对该细胞系的免疫表型、生物学、遗传学、分子特征和致瘤性进行了全面分析。PDAC-X2 细胞呈现上皮形态,表达细胞标志物(CK7 和 CK19)以及其他标志物(E-钙黏蛋白、波形蛋白、Ki-67、CEA 和 CA19-9)。细胞群体倍增时间平均约为 69 小时。在体内,PDAC-X2 细胞始终保持其致瘤性,达到 100%的肿瘤形成率。该细胞系的核型以四倍体为主,表现出复杂的遗传标记。值得注意的是,PDAC-X2 细胞对多种药物(包括吉西他滨、紫杉醇、5-氟尿嘧啶和奥沙利铂)表现出耐药性。总之,PDAC-X2 提供了一个非常有价值的临床前模型。它的用途在于促进耐药机制的研究和探索旨在改善这种肿瘤类型预后的替代治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5811/11035558/3832696825c3/41598_2024_56464_Fig1_HTML.jpg

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