The Differential Metabolic Response of Oral Squamous Cell Carcinoma Cells and Normal Oral Epithelial Cells to Cisplatin Exposure
Xun Chen,
Sufang Kuang,
Yi He,
Hongyu Li,
Chen Yi,
Yiming Li,
Chao Wang,
Guanhui Chen,
Shangwu Chen,
Dongsheng Yu
Affiliations
Xun Chen
Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510055, China
Sufang Kuang
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
Yi He
Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510055, China
Hongyu Li
Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510055, China
Chen Yi
Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510055, China
Yiming Li
Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510055, China
Chao Wang
Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510055, China
Guanhui Chen
Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510055, China
Shangwu Chen
Guangdong Key Laboratory of Pharmaceutical Functional Genes, State Key Laboratory for Biocontrol, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China
Dongsheng Yu
Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510055, China
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.
