The First Clinical Medical College of Lanzhou University, Lanzhou, China.
The Sixth Clinical Medical School of Guangzhou Medical University, Guangzhou, China.
Sci Rep. 2024 Nov 29;14(1):29661. doi: 10.1038/s41598-024-81392-0.
Distal cholangiocarcinoma is a rare and highly aggressive malignant tumor. The inherent tumor characteristics and growth pattern of cancer cells pose a challenge for diagnosis and treatment. Chemotherapy resistance leads to limited treatment options for patients with advanced cholangiocarcinoma. However, drug resistance studies in cholangiocarcinoma are often limited by the use of preclinical models that do not accurately replicate the essential features of the disease. In this study, we established and characterized a primary multidrug-resistant distal cholangiocarcinoma cell line, CBC3T-6. STR profiling indicated no evidence of cross-contamination. This cell line remains stable during long-term in vitro culture and is characterized by short doubling times and rapid subcutaneous tumor formation in mice. In addition, among the first-line anticancer drugs for cholangiocarcinoma, CBC3T-6 cells showed varying degrees of resistance to gemcitabine, oxaliplatin, cisplatin, and 5-FU. Whole exome sequencing analysis revealed that CBC3T-6 cells contained a variety of potentially pathogenic somatic cell mutations, such as TP53 and KRAS mutations. ABCB1 mutation as a possible therapeutic target for multidrug resistance. In conclusion, CBC3T-6 cells can be used as a useful tool to study the mechanism of cholangiocarcinoma and develop new therapeutic strategies for multidrug resistance.
远端胆管癌是一种罕见且高度侵袭性的恶性肿瘤。肿瘤固有特性和癌细胞的生长方式给诊断和治疗带来了挑战。化疗耐药导致晚期胆管癌患者的治疗选择有限。然而,胆管癌的耐药性研究通常受到临床前模型的限制,这些模型不能准确复制疾病的基本特征。在本研究中,我们建立并鉴定了一个原发性多药耐药性远端胆管癌细胞系 CBC3T-6。STR 谱分析表明没有交叉污染的证据。该细胞系在长期体外培养中保持稳定,并具有短的倍增时间和在小鼠中快速形成皮下肿瘤的特征。此外,在胆管癌的一线抗癌药物中,CBC3T-6 细胞对吉西他滨、奥沙利铂、顺铂和 5-FU 表现出不同程度的耐药性。全外显子组测序分析显示,CBC3T-6 细胞含有多种潜在致病性体细胞突变,如 TP53 和 KRAS 突变。ABCB1 突变可能是多药耐药的治疗靶点。总之,CBC3T-6 细胞可作为研究胆管癌机制和开发多药耐药新治疗策略的有用工具。