Zhang Yutao, Yang Yongming, Zan Likun, Wang Jing, Yan Lei, Zhao Lili, Chen Lixia, Xi Yanfeng, Bai Wenqi, Yang Xihua
Department of Colorectal and Anal Surgery, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, 030013, Taiyuan, Shanxi, China.
These authors contributed eqully to this work.
Iran J Basic Med Sci. 2023 Feb;26(2):248-254. doi: 10.22038/IJBMS.2022.67445.14780.
Patient-derived xenograft (PDX) model becomes a more and more important tool for tumor research. This study aimed to establish a colorectal cancer PDX model and verify its applicability.
Fresh human colorectal cancer tissue was surgically removed and subcutaneously inoculated into immunodeficient mice to establish the PDX model. Hematoxylin and eosin (HE) staining and immunohistochemical staining were used to evaluate the model. The successful PDX model was selected to study the efficacy of capecitabine in treating colorectal cancer.
HE staining showed that the PDX mice model of colorectal cancer could preserve the histological characteristics of the primary tumor. Immunohistochemistry staining showed α-fetoprotein (AFP), carcinoembryonic antigen (CEA), and E-cadherin were strongly positively expressed in primary human and PDX tumor tissues, with a high degree of similarity. Capecitabine significantly inhibited PDX tumor growth and reduced the expression of AFP and CEA proteins in the tumor tissues (all <0.05).
We successfully established a colorectal cancer PDX model, and the PDX model could retain the histological and biological characteristics of the primary tumor. Using this PDX model, we revealed that capecitabine at a dose of 300-400 mg/kg can effectively treat colorectal cancer, and no significant difference in toxicity was found among different dose groups. The current work provides a feasible framework for establishing and validating the PDX tumor model to better facilitate the evaluation of drug efficacy and safety.
患者来源的异种移植(PDX)模型成为肿瘤研究中越来越重要的工具。本研究旨在建立结直肠癌PDX模型并验证其适用性。
手术切除新鲜人结直肠癌组织,皮下接种于免疫缺陷小鼠建立PDX模型。采用苏木精-伊红(HE)染色和免疫组织化学染色评估该模型。选择成功的PDX模型研究卡培他滨治疗结直肠癌的疗效。
HE染色显示,结直肠癌PDX小鼠模型可保留原发肿瘤的组织学特征。免疫组织化学染色显示,甲胎蛋白(AFP)、癌胚抗原(CEA)和E-钙黏蛋白在人原发肿瘤组织和PDX肿瘤组织中均呈强阳性表达,相似度高。卡培他滨显著抑制PDX肿瘤生长,并降低肿瘤组织中AFP和CEA蛋白的表达(均P<0.05)。
我们成功建立了结直肠癌PDX模型,该模型可保留原发肿瘤的组织学和生物学特征。利用该PDX模型,我们发现300 - 400mg/kg剂量的卡培他滨可有效治疗结直肠癌,不同剂量组间毒性无显著差异。目前的工作为建立和验证PDX肿瘤模型提供了一个可行的框架,以更好地促进药物疗效和安全性的评估。