AbstractIn this study, we successfully established a novel gallbladder cancer cell line, designated as GBC-X1, derived from a primary tumor of a gallbladder cancer patient. By comprehensively analyzing the cell line’s phenotype, molecular characteristics, biomarkers, and histological characteristics, we confirmed that GBC-X1 serves as a valuable model for investigating the pathogenesis of gallbladder cancer and developing therapeutic agents.

摘要在这项研究中，我们成功建立了一种新的胆囊癌细胞系，命名为GBC-X1，来源于胆囊癌患者的原发肿瘤。通过综合分析细胞系的表型，分子特征，生物标志物和组织学特征，我们证实GBC-X1可作为研究胆囊癌发病机制和开发治疗剂的有价值模型。

GBC-X1 has been continuously cultured for one year, with over 60 stable passages. Morphologically, GBC-X1 exhibits typical features of epithelial tumors. The population doubling time of GBC-X1 is 32 h. STR analysis validated a high consistency between GBC-X1 and the patient’s primary tumor. Karyotype analysis revealed an abnormal hypertetraploid karyotype for GBC-X1, characterized by representative karyotypes of 98, XXXX del (4) p (12) del (5) p (21) der (10).

GBC-X1已连续培养一年，稳定传代60多次。形态学上，GBC-X1表现出上皮肿瘤的典型特征。GBC-X1的种群倍增时间为32小时。STR分析验证了GBC-X1与患者原发肿瘤之间的高度一致性。核型分析显示GBC-X1的异常四倍体核型，其特征是代表性核型为98xxxx del（4）p（12）del（5）p（21）der（10）。

Under suspension culture conditions, GBC-X1 efficiently forms tumor balls, while subcutaneous inoculation of GBC-X1 cells into NXG mice leads to xenograft formation with a rate of 80%. Drug sensitivity testing demonstrated that GBC-X1 is resistant to oxaliplatin and sensitive to 5-FU, gemcitabine, and paclitaxel.

在悬浮培养条件下，GBC-X1有效地形成肿瘤球，而将GBC-X1细胞皮下接种到NXG小鼠中导致异种移植物形成率为80%。药物敏感性测试表明，GBC-X1对奥沙利铂耐药，对5-FU，吉西他滨和紫杉醇敏感。

Immunohistochemistry revealed positive expression of CK7, CK19, E-cadherin, MMP-2, CD44, SOX2, and TP53 in GBC-X1 cells, weak positive expression of Vimentin, and a Ki67 positive rate of 35%. Our research highlights GBC-X1 as a novel gallbladder cancer cell line and emphasizes its potential as an effective experimental model for investigating the pathogenesis of gallbladder cancer and drug development..

免疫组织化学显示GBC-X1细胞中CK7，CK19，E-钙粘蛋白，MMP-2，CD44，SOX2和TP53阳性表达，波形蛋白弱阳性表达，Ki67阳性率为35%。我们的研究强调GBC-X1是一种新型胆囊癌细胞系，并强调其作为研究胆囊癌发病机制和药物开发的有效实验模型的潜力。。

IntroductionGallbladder cancer commonly originates from the mucosal epithelium of the gallbladder and represents the most prevalent and highly prognostically unfavorable malignant tumor in the biliary system1,2. In 2020, there were approximately 19.3 million newly diagnosed cancer cases worldwide, resulting in nearly 10 million cancer-related deaths.

引言胆囊癌通常起源于胆囊粘膜上皮，是胆道系统中最常见且预后最差的恶性肿瘤1,2。2020年，全世界约有1930万新诊断的癌症病例，导致近1000万癌症相关死亡。

Among these cases, gallbladder cancer accounted for 0.6% of newly diagnosed cancer patients and 0.9% of cancer-related deaths3. Gallbladder cancer has obvious geographical distribution characteristics, among which Bolivia in South America, Chile, northern India, Eastern Europe, and some Southeast Asian countries have higher incidence rate; The incidence rate is the lowest in European origin regions such as the United States, Australia, Canada, the United Kingdom and New Zealand4,5.

在这些病例中，胆囊癌占新诊断癌症患者的0.6%，占癌症相关死亡的0.9%3。胆囊癌具有明显的地理分布特征，其中玻利维亚在南美、智利、印度北部、东欧和一些东南亚国家的发病率较高；美国，澳大利亚，加拿大，英国和新西兰等欧洲起源地区的发病率最低4,5。

Gallbladder cancer is one of the few tumors showing global gender differences. The incidence rate of women is three to six times higher than that of men6. The overall incidence rate in China is about 3.82/100,000, of which the incidence rate in Shanghai can reach 7.8/100,000. In recent years, the incidence rate in China has been rising, causing more and more attention7,8.

胆囊癌是少数显示全球性别差异的肿瘤之一。女性的发病率是男性的三到六倍6。中国的总发病率约为3.82/10万，其中上海的发病率可达7.8/10万。近年来，中国的发病率一直在上升，引起越来越多的关注7,8。

Radical surgery remains the sole approach to achieving long-term survival for gallbladder cancer patients. However, this disease exhibits covert initial onset, marked malignancy, pronounced invasiveness, and a propensity for metastasis and dissemination. Early diagnosis is only possible for a meager 10–20% of patients9,10, with the majority being diagnosed at advanced stages, thus missing the opportunity for surgical intervention.

根治性手术仍然是实现胆囊癌患者长期生存的唯一方法。然而，这种疾病表现出隐蔽的初始发作，明显的恶性肿瘤，明显的侵袭性以及转移和传播的倾向。早期诊断仅适用于10-20%的患者9,10，其中大多数被诊断为晚期，因此错过了手术干预的机会。

The 5-year survival rate for patients with advanced gallbladder cancer ranges from a mere 5–15% 4,11.In 1980, Koyama established the world’s first gal.

晚期胆囊癌患者的5年生存率仅为5-15%4,11。1980年，Koyama建立了世界上第一个gal。

Data availability

数据可用性

The datasets used and/or analysed during the current study are available from the corresponding author upon reasonable request.

本研究中使用和/或分析的数据集可根据合理要求从通讯作者处获得。

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Download referencesAcknowledgementsWe would like to thank Bullet Edits (http://www.bulletedits.cn) for English language editing of the manuscript.Funding This work was supported by grants from National Natural Science Foundation of China(Grants 82260555 and 82360510), Natural Science Foundation of Gansu Province (Grants 22JR11RA022, 22JR5RA901, 23JRRA0929 and 23JRRA1601), Lanzhou Science and Technology Plan Project (Grants 2022-3-45 and 2023-2-38), Intra-Hospital Fund of the First Hospital of Lanzhou University (Grant ldyyyn2022-12 ), Chengguan District Science and Technology Plan (Grant 2023SHFZ0018).Author informationAuthor notesChangpeng Chai, Huan Tang, Xin Miao and Tingting Chen contributed equally to this work.Authors and AffiliationsThe Fourth Department of General Surgery, The First Hospital of Lanzhou University, No.

下载参考文献致谢我们要感谢项目符号编辑(http://www.bulletedits.cn)用于手稿的英文编辑。资助这项工作得到了国家自然科学基金（资助82260555和82360510），甘肃省自然科学基金（资助22JR11RA022、22JR5RA901、23JRRA0929和23JRRA1601），兰州科技计划项目（资助2022-3-45和2023-2-38），兰州大学第一医院院内基金（资助ldyyyn2022-12），城关区科技计划（资助2023SHFZ0018）的资助。作者信息作者注Chaang Peng Chai，Huan Tang，Xin Miao和Tingting Chen对这项工作做出了同样的贡献。作者和附属机构兰州大学第一医院第四普外科，No。

1, Donggang West Road, Lanzhou, 730000, Gansu, ChinaChangpeng Chai, Lu Li, Long Miao, Bo Zhang, Zhengfeng Wang, Wei Luo & Hao XuThe Second Clinical Medical College, Lanzhou University, Lanzhou, 730000, ChinaChangpeng Chai, Huan Tang, Tingting Chen, Yuanhui Su, Long Miao, Zhengfeng Wang, Hui Zhang & Wence ZhouState Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730000, ChinaXin MiaoFirst School of Clinical Medicine, Zhejiang Provincial Hospital of Chinese Medicine, Zhejiang Chinese Medical University, Hangzhou, 310006, ChinaXin Miao & Hao XuDepartment of General Surgery, Lanzhou University Second Hospital, No.

中国甘肃省兰州市东港西路1号，730000，兰州大学第二临床医学院，兰州，730000，兰州大学第二临床医学院，兰州，730000徐兰州大学第二医院普外科。

82 Cuiyingmen, Chengguan District, Lanzhou, 730000, ChinaHui Zhang & Wence ZhouThe First Clinical Medical College, Lanzhou University, Lanzhou, 730000, ChinaHao XuAuthorsChan.

中国兰州市城关区翠英门82号，730000，张辉，周文策兰州大学第一临床医学院，兰州，730000，许浩作者Chan。

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PubMed Google ScholarContributionsC.P.C, H.T, X.M , T.T.C and Y.H.S analyzed and interpreted the results of the detection of this novel cell line, and wrote a part of the manuscript. H.X, L.L, L.M and B.Z performed identification of the cell line, and were major contributors in writing the manuscript.

PubMed谷歌学术贡献中心。P、 C，H.T，X.M，T.T.C和Y.H.S分析并解释了这种新型细胞系的检测结果，并撰写了部分手稿。H、 X，L.L，L.M和B.Z进行了细胞系的鉴定，并且是撰写手稿的主要贡献者。

Z.F.W, W.L and H.Z were responsible for specimen collection. W.C.Z wrote part of the manuscript and modified the images and were involved in data processing. C.P.C, H.T, X.M, T.T.C and H.X performed the cell culture. C.P.C, H.T, X.M, Y.H.S, L.L produced the pathological sections. Z.F.W, W.L and H.Z organized the data for all the experiments.

Z、 F.W、W.L和H.Z负责标本采集。W、 C.Z写了部分手稿，修改了图像，并参与了数据处理。C、 P.C，H.T，X.M，T.T.C和H.X进行细胞培养。C、 P.C，H.T，X.M，Y.H.S，L.L产生病理切片。Z、 F.W，W.L和H.Z组织了所有实验的数据。

W.C.Z and H.X conceived and designed and supervised the study. All authors read and approved the final manuscript.Corresponding authorsCorrespondence to.

W、 C.Z和H.X构思、设计并监督了这项研究。所有作者都阅读并批准了最终手稿。通讯作者通讯。

Hao Xu or Wence Zhou.Ethics declarations

徐浩或周文策。道德宣言

Consent for publication

同意出版

We have obtained consents to publish this paper from all the participants of this study.

我们已获得本研究所有参与者的同意发表本文。

Competing interests

相互竞争的利益

The authors declare no competing interests.

作者声明没有利益冲突。

Ethical approval

道德认可

The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of Lanzhou University Second Hospital (2023 A-381). Informed consent was obtained from the patient. The animal procedures were approved by the Medical Animal Experiment Ethics Committee of Lanzhou University Second Hospital (D2023-318)..

该研究是根据《赫尔辛基宣言》的指导方针进行的，并经兰州大学第二医院伦理委员会（2023 A-381）批准。获得患者的知情同意。动物程序经兰州大学第二医院医学动物实验伦理委员会（D2023-318）批准。。

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Reprints and permissionsAbout this articleCite this articleChai, C., Tang, H., Miao, X. et al. Establishment and characterization of a novel human gallbladder cancer cell line, GBC-X1.

转载和许可本文引用本文Chai，C.，Tang，H.，Miao，X。等人。新型人胆囊癌细胞系GBC-X1的建立和表征。

Sci Rep 14, 21439 (2024). https://doi.org/10.1038/s41598-024-72830-0Download citationReceived: 13 April 2024Accepted: 11 September 2024Published: 13 September 2024DOI: https://doi.org/10.1038/s41598-024-72830-0Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

科学报告1421439（2024）。https://doi.org/10.1038/s41598-024-72830-0Download引文接收日期：2024年4月13日接受日期：2024年9月11日发布日期：2024年9月13日OI：https://doi.org/10.1038/s41598-024-72830-0Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

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KeywordsGallbladder cancerCell lineEstablishmentDrug resistance

关键词全膀胱癌细胞系建立耐药性

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