Abstract
Colorectal cancer is the second most common cancer in women, the third in men, and an important cause of cancer-related mortality. Recurrence and the development of chemotherapy resistance are major hindrances for patients’ treatment. The presence of cancer stem cells with chemotherapy resistance able to generate proliferating tumor cells contributes to tumor recurrence and resistance. In addition, tumor cells can develop chemoresistance through adaptation mechanisms. In this article, cancer stem cells were isolated from HT29 and SW620 colorectal cancer cell lines. Oxaliplatin resistance was induced by a single drug treatment simulating the usual guidelines of patient treatment. A comparison of these two populations showed similarities since cancer stem cells presented increased oxaliplatin resistance, and resistant cells contained an increased number of cancer stem cells. Cancer stem cells isolated from resistant cells showed increased oxaliplatin resistance. Cell invasion capacity and epithelial-mesenchymal transition were increased both in cancer stem cells and oxaliplatin-resistant cells. mRNA expression analysis showed that both cell types shared a significant proportion of commonly regulated genes. In summary, the data presented indicate that colorectal cancer stem cells and oxaliplatin-resistant cells are highly related cell populations that might have interesting implications in the development of tumor recurrence and resistance to chemotherapy.
Highlights
Colorectal cancer (CRC) is the fifth most common type of cancer, with nearly 1.1 million cases diagnosed in 2020 around the world
The human colon adenocarcinoma cell line HT29 and the colorectal adenocarcinoma cell line SW620 were cultured under non-adherent conditions in a defined, serum-free medium (3D culture) in order to select spheroid-forming cancer stem cells
The percentage of cancer stem cells (CSCs) in the HT29 cell line was very high (72.46%) and much larger than that observed in SW620 cells (13.38%)
Summary
Colorectal cancer (CRC) is the fifth most common type of cancer, with nearly 1.1 million cases diagnosed in 2020 around the world. It is the third most common cancer in men and the second in women. Standard first- and second-line treatments of CRC are based on the combination of 5fluorouracil plus oxaliplatin or irinotecan [4]. This combined treatment produces response rates of 40–50% in the patients [5]; many patients do not respond to chemotherapy, presenting a low overall survival [6]
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