Frontiers in Oncology (Jun 2021)
EMT and Cancer Cell Stemness Associated With Chemotherapeutic Resistance in Esophageal Cancer
- Xiaojie Liu,
- Xiaojie Liu,
- Xiaojie Liu,
- Mingjing He,
- Mingjing He,
- Mingjing He,
- Linlin Li,
- Linlin Li,
- Linlin Li,
- Xiya Wang,
- Xiya Wang,
- Xiya Wang,
- Shuhua Han,
- Shuhua Han,
- Shuhua Han,
- Jinzhu Zhao,
- Jinzhu Zhao,
- Jinzhu Zhao,
- Yalong Dong,
- Yalong Dong,
- Yalong Dong,
- Mushtaq Ahmad,
- Mushtaq Ahmad,
- Mushtaq Ahmad,
- Leilei Li,
- Leilei Li,
- Leilei Li,
- Xueyan Zhang,
- Xueyan Zhang,
- Xueyan Zhang,
- Junfeng Huo,
- Junfeng Huo,
- Junfeng Huo,
- Yunfan Liu,
- Chengxue Pan,
- Chengxue Pan,
- Cong Wang,
- Cong Wang,
- Cong Wang
Affiliations
- Xiaojie Liu
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
- Xiaojie Liu
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, China
- Xiaojie Liu
- Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou, China
- Mingjing He
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
- Mingjing He
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, China
- Mingjing He
- Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou, China
- Linlin Li
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
- Linlin Li
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, China
- Linlin Li
- Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou, China
- Xiya Wang
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
- Xiya Wang
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, China
- Xiya Wang
- Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou, China
- Shuhua Han
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
- Shuhua Han
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, China
- Shuhua Han
- Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou, China
- Jinzhu Zhao
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
- Jinzhu Zhao
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, China
- Jinzhu Zhao
- Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou, China
- Yalong Dong
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
- Yalong Dong
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, China
- Yalong Dong
- Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou, China
- Mushtaq Ahmad
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
- Mushtaq Ahmad
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, China
- Mushtaq Ahmad
- Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou, China
- Leilei Li
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
- Leilei Li
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, China
- Leilei Li
- Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou, China
- Xueyan Zhang
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
- Xueyan Zhang
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, China
- Xueyan Zhang
- Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou, China
- Junfeng Huo
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
- Junfeng Huo
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, China
- Junfeng Huo
- Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou, China
- Yunfan Liu
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
- Chengxue Pan
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
- Chengxue Pan
- Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou, China
- Cong Wang
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
- Cong Wang
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, China
- Cong Wang
- Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou, China
- DOI
- https://doi.org/10.3389/fonc.2021.672222
- Journal volume & issue
-
Vol. 11
Abstract
Drug resistance often occurs after chemotherapy in esophageal cancer patients, leading to cancer metastasis and recurrence. However, the relationship among cancer cell migration, recurrence and drug resistance in esophageal cancer drug-resistant cells has not been clearly explained. In this study, we constructed paclitaxel (PTX)-resistant esophageal cancer cells to explore the causes of drug resistance and poor prognosis after chemotherapy in esophageal cancer. Colony formation assay was used to evaluate the difference of colony formation between parental cells and drug resistance cells. Microsphere formation assay was used to examine the phenotype of stem cells. Wound healing and Transwell assays were used to detect the migration ability of drug-resistant cells. Western blotting and immunofluorescence assays were used to explore the mechanisms. Finally, we used nude mouse xenograft model to explore the tumor characteristics and the expression of relative proteins to verify our findings in vivo. Our study demonstrated that the cancer cell stemness characteristics exist in drug-resistant esophageal cancer cells, that expressed the biomarkers of stem cells and were prone to epithelial-mesenchymal transition (EMT). Our results suggested that the expression of EMT biomarkers and stemness-related proteins increased in esophageal cancer cells after continuously using chemotherapeutic drugs for a period of time. This study indicated that simultaneously targeting EMT and stemness could be a better strategy for the treatment of esophageal cancer drug resistance.
Keywords