Binbin Wei1, Congfei Wang2, Tianhong Teng2, Pengfei Guo1, Minghuang Chen3, Feng Xia1, Huili Liu4, Jieming Xie5, Jianghua Feng1, Heguang Huang2. 1. Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen, China. 2. Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China. 3. State Structural Chemistry Key Laboratory of Fujian Institute of Research on Structure of Matter, Chinese Academy of Sciences, Fuzhou, China. 4. State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Center for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, China. 5. Department of Pharmacology, Fujian Medical University, Fuzhou, China.
Abstract
BACKGROUND: As the preferred drug for single chemotherapeutic application in pancreatic cancer, gemcitabine often demonstrated low sensitivity and strong chemotherapy resistance in patients. Therefore, the search for other drugs with high efficiency and low side effects has become of high importance. The aim of this study was to assess the therapeutic effects of cucurmosin on pancreatic cancer as an alternative of gemcitabine and explore its underlying biochemical mechanism. METHODS: The subcutaneous xenograft mice with pancreatic cancer were treated by high- and low-dose cucurmosin and gemcitabine, respectively. A comparative metabolomic analysis was performed on the serum samples from the different groups by 1H nuclear magnetic resonance (NMR) techniques and then subjected to univariate and multivariate statistical analysis. RESULTS: Cucurmosin demonstrated a dose-dependent inhibition to the pancreatic tumors. High-dose cucurmosin provided similar chemotherapeutic efficacy with gemcitabine by positively regulating pyruvate metabolism, glycolysis or gluconeogenesis, and cysteine and methionine metabolism. Inactivating GFR signaling pathway and further inducing apoptosis of tumor cells are the important mechanism of anti-tumor function of cucurmosin. CONCLUSIONS: Cucurmosin is a promising chemotherapeutic drug for pancreatic cancer. However, the dose selection and surface modification should be optimized according to the stage of pancreatic cancer, and an expanded study in both laboratory and clinical regimes needs to be performed. 2020 Gland Surgery. All rights reserved.
BACKGROUND: As the preferred drug for single chemotherapeutic application in pancreatic cancer, gemcitabine often demonstrated low sensitivity and strong chemotherapy resistance in patients. Therefore, the search for other drugs with high efficiency and low side effects has become of high importance. The aim of this study was to assess the therapeutic effects of cucurmosin on pancreatic cancer as an alternative of gemcitabine and explore its underlying biochemical mechanism. METHODS: The subcutaneous xenograft mice with pancreatic cancer were treated by high- and low-dose cucurmosin and gemcitabine, respectively. A comparative metabolomic analysis was performed on the serum samples from the different groups by 1H nuclear magnetic resonance (NMR) techniques and then subjected to univariate and multivariate statistical analysis. RESULTS: Cucurmosin demonstrated a dose-dependent inhibition to the pancreatic tumors. High-dose cucurmosin provided similar chemotherapeutic efficacy with gemcitabine by positively regulating pyruvate metabolism, glycolysis or gluconeogenesis, and cysteine and methionine metabolism. Inactivating GFR signaling pathway and further inducing apoptosis of tumor cells are the important mechanism of anti-tumor function of cucurmosin. CONCLUSIONS: Cucurmosin is a promising chemotherapeutic drug for pancreatic cancer. However, the dose selection and surface modification should be optimized according to the stage of pancreatic cancer, and an expanded study in both laboratory and clinical regimes needs to be performed. 2020 Gland Surgery. All rights reserved.
Entities:
Keywords:
Cucurmosin (CUS); chemotherapeutic drug; metabolomics; pancreatic cancer
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