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