高等学校化学学报

高等学校化学学报

• 研究论文 • 上一篇    下一篇

结直肠癌野生型和耐药型细胞系之间的基因表达状态的比较分析

于成鲲1,2，周海超3,4，张聪敏4，任  艳2,5，刘斯奇2,4   

  1. 1. 浙江工业大学药学院

    2. 中国科学院杭州医学所

    3. 中国科学院大学生命科学学院

    4. 华大基因科技有限公司 5. 上海中医药大学科技实验中心

  • 收稿日期:2025-02-24 修回日期:2025-04-18 网络首发:2025-04-21 发布日期:2025-04-21
  • 通讯作者: 刘斯奇 E-mail:siqiliu@genomics.cn
  • 基金资助:
    浙江省“尖兵”“领雁”研发攻关计划(批准号：2023C03103)资助

A Comprehensive Analysis of the Gene Expression Status in Wild and Drug-resistance Cell Lines of Colorectal Cancer

YU Chengkun1,2, ZHOU Haichao3,4, ZHANG Congmin4, REN Yan2,5, LIU Siqi2,4*   

  1. 1. College of Pharmacy Science, Zhejiang University of Technology

    2. Hangzhou Institute of Medicine, Chinese Academy of Science

    3. College of Life Science, University of Chinese Academy of Sciences

    4. Beijing Genomics Institute Technology Co., Ltd,

    5. Science of Technology Experimental Center, Shanghai University ofTraditional Chinese Medicine

  • Received:2025-02-24 Revised:2025-04-18 Online First:2025-04-21 Published:2025-04-21
  • Contact: LIU Siqi E-mail:siqiliu@genomics.cn
  • Supported by:
    Supported by "Pioneer" and "Leading Goose" R&D Program of Zhejiang Province (No. 2023C03103)

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摘要： 本研究对3种结直肠癌细胞系 (HCT116、LoVo、HT29)的野生株和Oxaliplatin /SN38耐药株的转录组和蛋白质组分别进行了检测，通过分析野生株和耐药株基因表达的差异，发现：在Oxaliplatin耐药细胞系中，3种细胞系的转录组响应较为一致；但在SN38耐药细胞系中，HT29细胞系转录组响应模式与其它2个细胞系显著不同. 野生株和耐药株之间的蛋白质组比较分析显示，发生变化的蛋白质与转录本有较大程度的重合；与转录组数据不同的是，LoVo和HT29的蛋白质丰度受药物的影响较大，但从差异蛋白质功能聚类来看，LoVo和HCT116呈现相似性. 比较分析还表明，Oxaliplatin在3个细胞系中所引发蛋白质丰度响应明显低于SN38造成的蛋白质丰度变化. 从野生型和耐药型的结肠癌细胞系的转录组和蛋白质组的整合分析出发，获得了新的候选耐药性相关蛋白.本研究可能为结直肠癌耐药性机制研究奠定了坚实的实验数据，提供了另一种启发性的思路.

关键词: 结直肠癌, 奥沙利铂, SN38, 耐药性

Abstract: This study examined 3 colorectal cancer cell lines—HCT116, LoVo, and HT29—each of which contained both wild-type and Oxaliplatin/SN38-resistant strains. Transcriptomic and proteomic analyses were performed. By analyzing the differential gene expression between wild-type and resistant strains, it was found that the transcriptomic patterns of HCT116 and LoVo wild-type cell line appeared similar, whereas both were different from HT29. In view of different expression genes (DEGs) of the cell lines responding to oxaliplatin or SN38, the transcriptomes of wild cell lines were different from that obtained from the drug resistant cell lines. Moreover, among oxaliplatin resistant cell lines, the transcriptomic responses were consistent, but in SN38 resistant cell lines, the relevant changes were complicated, particularly in HT29 cells. Based on comparison of different expression proteins (DEPs) in these cells, DEPs were overlapped with DEGs somehow. In contrast to transcriptomes, the protein abundance in Lovo and HT29 was sensitively impacted by drugs, while the functional clustering derived from DEPs in LoVo and HCT116 was comparable. By analyzing the commonly regulated genes in both the transcriptome and proteome, we identified candidate drug resistance-related proteins. Specifically for drugs, the abundance responses of proteins in these cell lines initiated by oxaliplatin were significantly lower than these induced by SN38. Taking all analysis to gene expression status in wild and drug resistance cell lines together, this study indeed sets up a solid dataset to explore the molecular mechanism of drug resistance and provides an omic clue in colorectal cancer research.

Key words: Colorectal cancer, Oxaliplatin, SN38, Drug resistance

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