基于UPLC-MS技术的紫草素干预结肠癌移植瘤小鼠血清代谢组学研究

Effects of shikonin on colon cancer xenografts in nude mice based on serum metabolomics

研究萘醌类化合物紫草素(shikonin)体外抗肿瘤活性与对SW620结肠癌移植瘤小鼠的抗肿瘤作用及其机制。采用MTT法测定紫草素对4种结直肠癌细胞的半数抑制浓度(IC50);建立人结肠癌SW620裸鼠异体移植瘤模型,通过测定肿瘤体积、抑瘤率观察紫草素在体内的抗肿瘤活性并利用代谢组学技术结合多元统计对小鼠血清进行分析,探讨紫草素抗肿瘤作用机制。结果显示,紫草素能够显著抑制4种结肠癌细胞的增殖,同时在体内具有较高的抗肿瘤活性,在低、高剂量条件下抑瘤率分别达38.35%和42.16%。代谢组学分析共鉴定出包括色氨酸、缬氨酸和甲硫氨酸在内的38个差异代谢物,通路富集发现其主要通过调节SW620结肠癌移植瘤小鼠体内紊乱的氨基酸代谢发挥抗肿瘤作用,其中对色氨酸代谢通路的影响最为显著。本研究表明紫草素能够通过调节氨基酸代谢发挥抗结肠癌作用,为紫草素的进一步开发及临床应用提供理论依据。

To investigate the antitumor activity of shikonin against human colorectal cancer, the IC50 value towards four different human colon cancer cells was detected by MTT assay. In addition, a SW620 xenograft model was established and both the tumor volume and tumor inhibitory rate were calculated to evaluate the antitumor activity of shikonin in vivo. To further explore the mechanism of shikonin, metabolomics combined with multivariate statistical analysis was performed to analyse the profile of metabolites in mouse serum. The results show that shikonin can significantly inhibit the proliferation of four different colon cancer cell lines and exerted a high antitumor activity in vivo. The tumor inhibitory rate at low dose and high dose were 38.35% and 42.16%, respectively. In addition, a total of 38 potential biomarkers related to the antitumor effects of shikonin were identified through metabolomics analysis, including tryptophan, proline and methionine. The study revealed that the mechanism was related to disordered amino acid metabolism in colon cancer, especially in tryptophan metabolism. Our study suggests that shikonin could exert an antitumor effect by regulating amino acid metabolism in colon cancer and provides a theoretical foundation for further exploration and the eventual clinical application of shikonin.