DEHP mediates drug resistance by metabolic reprogramming in colorectal cancer cells

• DOI: 10.1007/s11356-022-25110-1
• Publication Date: 2023-02-07T11:23:08Z
• Authors: Yue Wu; Ruijie Lu; Yujie Lin; Jinjin Wang; Zijian Lou; Xiaochun Zheng; Ling Zhang; Ruolang Pan; Gang Lu; Qingxia Fang
• Keywords: Mice; Plasticizers; Diethylhexyl Phthalate; Humans; Animals; Insulin Resistance; Colorectal Neoplasms; 01 natural sciences; 3. Good health; Research Article; 0105 earth and related environmental sciences

AbstractLong-term exposure to diethylhexyl phthalate (DEHP), an endocrine-disrupting chemical (EDCs) and plasticizer widely used in consumer products, has been reported to be significantly positively correlated with increased risks of different human diseases, including various cancers, while the potential effect of DEHP on colorectal cancer progression was little studied. In the present study, we showed that DEHP could trigger the metabolic reprogramming of colorectal cancer cells, promote cell growth and decrease fluorouracil (5-FU) sensitivity. Mechanistic studies indicated that DEHP could reduce glycolysis activity and increase oxidative phosphorylation (OXPHOS) in SW620 cells. In addition, in vivo experiments showed that DEHP promoted tumorigenic progression and decreased survival time in mice. Collectively, our findings suggest that DEHP may be a potent risk factor for colorectal cancer development.