Intracellular magnetic hyperthermia reverses sorafenib resistance in hepatocellular carcinoma through its action on signaling pathways
Hugang Li,
Zirui Ye,
Xun Wang,
Jianlan Yuan,
Jingyi Guo,
Chen Liu,
Bin Yan,
Haiming Fan,
Yi Lyu,
Xiaoli Liu
Affiliations
Hugang Li
National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine; Shaanxi Province Center for Regenerative Medicine and Surgery Engineering Research; Shaanxi Provincial Key Laboratory of Magnetic Medicine; First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China; School of Future Technology, Xi’an Jiaotong University, Xi’an, Shaanxi 710049, China
Zirui Ye
National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine; Shaanxi Province Center for Regenerative Medicine and Surgery Engineering Research; Shaanxi Provincial Key Laboratory of Magnetic Medicine; First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China; Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710049, China
Xun Wang
Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education; Provincial Key Laboratory of Biotechnology of Shaanxi Province, Northwest University, Xi’an, Shaanxi 710069, China
Jianlan Yuan
Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education; Provincial Key Laboratory of Biotechnology of Shaanxi Province, Northwest University, Xi’an, Shaanxi 710069, China
Jingyi Guo
Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education; Provincial Key Laboratory of Biotechnology of Shaanxi Province, Northwest University, Xi’an, Shaanxi 710069, China
Chen Liu
Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education; Provincial Key Laboratory of Biotechnology of Shaanxi Province, Northwest University, Xi’an, Shaanxi 710069, China
Bin Yan
National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine; Shaanxi Province Center for Regenerative Medicine and Surgery Engineering Research; Shaanxi Provincial Key Laboratory of Magnetic Medicine; First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China; Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710049, China; Corresponding author
Haiming Fan
Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education; Provincial Key Laboratory of Biotechnology of Shaanxi Province, Northwest University, Xi’an, Shaanxi 710069, China; Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi’an 710127, China
Yi Lyu
National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine; Shaanxi Province Center for Regenerative Medicine and Surgery Engineering Research; Shaanxi Provincial Key Laboratory of Magnetic Medicine; First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China; Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710049, China; School of Future Technology, Xi’an Jiaotong University, Xi’an, Shaanxi 710049, China; Corresponding author
Xiaoli Liu
National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine; Shaanxi Province Center for Regenerative Medicine and Surgery Engineering Research; Shaanxi Provincial Key Laboratory of Magnetic Medicine; First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China; Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710049, China; School of Future Technology, Xi’an Jiaotong University, Xi’an, Shaanxi 710049, China; Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education; Provincial Key Laboratory of Biotechnology of Shaanxi Province, Northwest University, Xi’an, Shaanxi 710069, China; Corresponding author
Summary: Sorafenib, a first-line drug for advanced hepatocellular carcinoma (HCC), unfortunately encounters resistance in most patients, leading to disease progression. Traditional approaches to counteract this resistance, particularly those targeting the RAF-MEK-ERK pathway, often face clinical feasibility limitations. Magnetic hyperthermia (MH), unlike conventional thermal therapies, emerges as a promising alternative. It uniquely combines magnetothermal effects with an increase in reactive oxygen species (ROS). This study found the potential of intracellular MH enhanced the efficacy of sorafenib, increased cellular sensitivity to sorafenib, and reversed sorafenib resistance by inhibiting the RAF-MEK-ERK pathway in an ROS-dependent manner in a sorafenib-resistant HCC cell. Further, in a sorafenib-resistant HCC mouse model, MH significantly sensitized tumors to sorafenib therapy, resulting in inhibited tumor growth and improved survival rates. This presents a promising strategy to overcome sorafenib resistance in HCC, potentially enhancing therapeutic outcomes for patients with this challenging condition.
