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建立和鉴定 18 个人结直肠癌细胞系。

Establishment and characterization of 18 human colorectal cancer cell lines.

机构信息

Korean Cell Line Bank, Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, 03080, Korea.

Cancer Research Institute, Seoul National University College of Medicine, Seoul, 03080, Korea.

出版信息

Sci Rep. 2020 Apr 22;10(1):6801. doi: 10.1038/s41598-020-63812-z.

Abstract

Colorectal cancer (CRC) represents the third most frequently diagnosed malignancy worldwide and is the second most common cause of tumor-associated mortalities in Korea. Due to the disease's aggressive behavior, the 5-year survival rate for CRC patients remains unpromising. Well-characterized cell lines have been used as a biological model for studying the biology of cancer and developing novel therapeutics. To assist in vitro studies, 18 CRC cell lines (SNU-1566, SNU-1983, SNU-2172, SNU-2297, SNU-2303, SNU-2353B, SNU-2359, SNU-2373B, SNU-2407, SNU-2423, SNU-2431, SNU-2465, SNU-2493, SNU-2536C, SNU-2621B, SNU-NCC-61, SNU-NCC-376, and SNU-NCC-377) derived from Korean patients were established and characterized in the present study. General characteristics of each cell line including doubling time, in vitro morphology, mutational profiles, and protein expressions of CRC-related genes were described. Whole exome sequencing was performed on each cell line to configure mutational profiles. Single nucleotide variation, frame shift, in-frame deletions and insertions, start codon deletion, and splice stop codon mutation of various genes were found and classified based on their pathogenicity reports. In addition, cell viability was assayed to measure their sensitivities to 24 anti-cancer drugs including anti-metabolites, kinase inhibitors, histone deacetylase inhibitors, alkylating inhibitors, and topoisomerase inhibitors, all widely used for various cancers. On testing, five CRC cell lines showed MSI, of which MLH1 or MSH6 gene was mutated. These newly established CRC cell lines can be used to investigate biological characteristics of CRC, particularly for investigating gene alterations associated with CRC.

摘要

结直肠癌(CRC)是全球发病率第三高的恶性肿瘤,也是韩国肿瘤相关死亡的第二大主要原因。由于该疾病具有侵袭性,CRC 患者的 5 年生存率仍不乐观。特征明确的细胞系已被用作癌症生物学研究和新型治疗药物开发的生物模型。为了辅助体外研究,本研究建立并鉴定了 18 株源自韩国患者的 CRC 细胞系(SNU-1566、SNU-1983、SNU-2172、SNU-2297、SNU-2303、SNU-2353B、SNU-2359、SNU-2373B、SNU-2407、SNU-2423、SNU-2431、SNU-2465、SNU-2493、SNU-2536C、SNU-2621B、SNU-NCC-61、SNU-NCC-376 和 SNU-NCC-377)。描述了每个细胞系的一般特征,包括倍增时间、体外形态、CRC 相关基因的突变谱和蛋白表达。对每个细胞系进行全外显子测序以构建突变谱。发现并根据其致病性报告对各种基因的单核苷酸变异、移码突变、框内缺失和插入、起始密码子缺失以及剪接终止密码子突变进行分类。此外,还通过细胞活力测定法检测了它们对包括抗代谢物、激酶抑制剂、组蛋白去乙酰化酶抑制剂、烷化剂抑制剂和拓扑异构酶抑制剂在内的 24 种抗癌药物的敏感性,这些药物广泛用于各种癌症的治疗。在测试中,有 5 株 CRC 细胞系表现出微卫星不稳定性,其中 MLH1 或 MSH6 基因发生突变。这些新建立的 CRC 细胞系可用于研究 CRC 的生物学特性,特别是研究与 CRC 相关的基因改变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dd2/7176734/6bb7277e95c0/41598_2020_63812_Fig1_HTML.jpg

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