Chen Xun, Kuang Sufang, He Yi, Li Hongyu, Yi Chen, Li Yiming, Wang Chao, Chen Guanhui, Chen Shangwu, Yu Dongsheng
Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510055, China.
Center for Proteomics and Metabolomics, State Key Laboratory of Biocontrol, Guangdong Province Key Laboratory for Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Metabolites. 2022 Apr 25;12(5):389. doi: 10.3390/metabo12050389.
Metabolic reprogramming is one of the hallmarks of a tumor. It not only promotes the development and progression of tumor but also contributes to the resistance of tumor cells to chemotherapeutics. The difference in the metabolism between drug-resistant and sensitive tumor cells indicates that drug-resistant tumor cells have experienced metabolic adaptation. The metabolic response induced by chemotherapy is dynamic, but the early metabolic response of tumor cells to anticancer drugs and the effect of an initial response on the development of drug resistance have not been well studied. Early metabolic intervention may prevent or slow down the development of drug resistance. The differential metabolic responses of normal cells and tumor cells to drugs are unclear. The specific metabolites or metabolic pathways of tumor cells to chemotherapeutic drugs can be used as the target of metabolic intervention in tumor therapy. In this study, we used comparative metabolomics to analyze the differential metabolic responses of oral cancer cells and normal oral epithelial cells to short-term cisplatin exposure, and to identify the marker metabolites of early response in oral cancer cells. Oral cancer cells showed a dynamic metabolic response to cisplatin. Seven and five metabolites were identified as specific response markers to cisplatin exposure in oral cancer cell SCC-9 and normal oral epithelial cell HOEC, respectively. Glyoxylate and dicarboxylate metabolism and fructose, malate, serine, alanine, sorbose and glutamate were considered as specific enriched metabolic pathways and biomarkers of SCC-9 cells in response to cisplatin, respectively. The existence of differential metabolic responses lays a foundation for tumor chemotherapy combined with metabolic intervention.
代谢重编程是肿瘤的特征之一。它不仅促进肿瘤的发生发展，还导致肿瘤细胞对化疗药物产生耐药性。耐药肿瘤细胞与敏感肿瘤细胞之间的代谢差异表明，耐药肿瘤细胞经历了代谢适应。化疗诱导的代谢反应是动态的，但肿瘤细胞对抗癌药物的早期代谢反应以及初始反应对耐药性发展的影响尚未得到充分研究。早期代谢干预可能预防或减缓耐药性的发展。正常细胞和肿瘤细胞对药物的差异代谢反应尚不清楚。肿瘤细胞对化疗药物的特定代谢产物或代谢途径可作为肿瘤治疗中代谢干预的靶点。在本研究中，我们采用比较代谢组学分析口腔癌细胞和正常口腔上皮细胞对短期顺铂暴露的差异代谢反应，并鉴定口腔癌细胞早期反应的标志物代谢产物。口腔癌细胞对顺铂表现出动态代谢反应。在口腔癌细胞SCC-9和正常口腔上皮细胞HOEC中，分别有7种和5种代谢产物被鉴定为对顺铂暴露的特异性反应标志物。乙醛酸和二羧酸代谢以及果糖、苹果酸、丝氨酸、丙氨酸、山梨糖和谷氨酸分别被认为是SCC-9细胞对顺铂反应的特异性富集代谢途径和生物标志物。差异代谢反应的存在为肿瘤化疗联合代谢干预奠定了基础。
