Department of Biochemistry, Faculty of Medical Science, Naresuan University, Phitsanulok, Thailand.
School of Science, Mae Fah Luang University, Chaiang Rai, Thailand.
Asian Pac J Cancer Prev. 2020 Jun 1;21(6):1739-1746. doi: 10.31557/APJCP.2020.21.6.1739.
Resistance to chemotherapeutic agents is usually found in cancer stem cells (CSCs) and cancer stem-like cells that are often regarded as the target for cancer monitoring. However, the different patterns of their transcriptomic profiling is still unclear.
This study aims to illustrate the transcriptomic profile of CSCs and butyrate-resistant colorectal carcinoma cells (BR-CRCs), by comparing them with parental colorectal cancer (CRC) cells in order to identify distinguishing transcription patterns of the CSCs and BR-CRCs.
Parental CRC cells HCT116 (HCT116-PT) were cultured and induced to establish the butyrate resistant cell model (HCT116-BR). Commercial enriching of the HCT116-CSCs were grown in a tumorsphere suspension culture, which was followed firstly by the assessment of butyrate tolerance using MTT and PrestoBlue. Then their gene expression profiling was analyzed by microarray.
The results showed that both butyrate-resistant HCT116 cells (HCT116-BR) and HCT116-CSCs were more tolerant a butyrate effects than HCT116-PT cells. Differentially expressed gene profiles exhibited that IFI27, FOXQ1, PRF1, and SLC2A3 genes were increasingly expressed in CSCs, and were dramatically overexpressed in HCT116-BR cells when compared with HCT116-PT cells. Moreover, PKIB and LOC399959 were downregulated both in HCT116-CSCs and HCT116-BR cells.
Our findings shed light on the transcriptomic profiles of chemoresistant CRC cells. This data should be useful for further study to provide guidelines for clinical prognosis to determine the guidelines for CRC treatment, especially in patients with chemoresistance and designing novel anti-neoplastic agents.
化疗药物耐药通常存在于癌症干细胞(CSC)和癌症干细胞样细胞中,这些细胞通常被认为是癌症监测的靶点。然而,它们的转录组谱模式仍不清楚。
本研究旨在通过比较CSC 和丁酸耐药结直肠癌细胞(BR-CRC)与亲本结直肠癌细胞(CRC),阐明 CSC 和 BR-CRC 的转录组谱,以确定 CSC 和 BR-CRC 的转录模式。
培养亲本 CRC 细胞 HCT116(HCT116-PT),并建立丁酸耐药细胞模型(HCT116-BR)。采用肿瘤球体悬浮培养法富集 HCT116-CSCs,首先用 MTT 和 PrestoBlue 评估丁酸耐受性,然后用微阵列分析其基因表达谱。
结果表明,丁酸耐药 HCT116 细胞(HCT116-BR)和 HCT116-CSCs 比 HCT116-PT 细胞对丁酸的作用更耐受。差异表达基因谱显示,IFI27、FOXQ1、PRF1 和 SLC2A3 基因在 CSCs 中表达增加,与 HCT116-PT 细胞相比,在 HCT116-BR 细胞中显著过表达。此外,PKIB 和 LOC399959 在 HCT116-CSCs 和 HCT116-BR 细胞中均下调。
我们的研究结果揭示了结直肠癌细胞耐药的转录组谱。这些数据对于进一步的研究提供了指导,有助于临床预后的确定,为结直肠癌的治疗提供指导,特别是在化疗耐药的患者中,并为设计新型抗肿瘤药物提供依据。