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.

Highlights

  • Colorectal cancer (CRC) represents the third most frequently diagnosed malignancy worldwide and is the second most common cause of tumor-associated mortalities in Korea

  • 25% of CRC cases are diagnosed in stage IV, and recurrence with distance metastasis follows after primary resection in nearly 50% of CRC patients[3]

  • While roughly 50% of CRC patients respond to customary chemotherapy, the majority develop drug resistance through the course of treatment, and relapse or distance metastasis often follows

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Summary

Introduction

Colorectal cancer (CRC) represents the third most frequently diagnosed malignancy worldwide and is the second most common cause of tumor-associated mortalities in Korea. The 24 drugs are categorized as anti-metabolites (TAS-102, Capecitabine, 5-FU), kinase inhibitors (Regorafenib, Apitolisib, MK-5108, AZD2014, Afatinib, Buparlisib, Trametinib), histone deacetylase inhibitors (Belinostat, SAHA), alkylating inhibitors (Oxaliplatin), topoisomerase inhibitors (Irinotecan), growth factor receptor inhibitors (Cetuximab, Bevacizumab), natural compounds (Resveratrol, Curcumin, Baicalein, Genistein), and miscellaneous (Lecouvorin calcium, ICG-001, Olaparib). These newly established 18 cell lines can be used to study the molecular biology of CRC, to investigate genomic alterations related to CRC

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