Abnormal activation of the Ras/Raf/Mek/Erk signaling cascade plays an important role in glioma. Inhibition of this aberrant activity could effectively hinder glioma cell proliferation and promote cell apoptosis. To in...Abnormal activation of the Ras/Raf/Mek/Erk signaling cascade plays an important role in glioma. Inhibition of this aberrant activity could effectively hinder glioma cell proliferation and promote cell apoptosis. To investigate the mechanism of gJioblastoma treatment by neural stem ceiJ trans- plantation with respect to the Ras/Raf/Mek/Erk pathway, C6 glioma cells were prepared in sus- pension and then infused into the rat brain to establish a glioblastoma model. Neural stem cells isolated from fetal rats were then injected into the brain of this glioblastoma model. Results showed that Raf-1, Erk and Bcl-2 protein expression significantly increased, while Caspase-3 protein expression decreased. After transplantation of neural stem cells, Raf-1, Erk and Bcl-2 protein expression significantly decreased, while Caspase-3 protein expression significantly in-creased. Our findings indicate that transplantation of neural stem cells may promote apoptosis of glioma cells by inhibiting Ras/Raf/Mek/Erk signaling, and thus may represent a novel treatment approach for glioblastoma.展开更多
The occurrence and development of cancer are closely related to dysregulation of cholesterol metabolism.Therefore,targeting cholesterol metabolism presents a novel diagnosis and treatment strategy for cancer.In this s...The occurrence and development of cancer are closely related to dysregulation of cholesterol metabolism.Therefore,targeting cholesterol metabolism presents a novel diagnosis and treatment strategy for cancer.In this study,a nanosystem(AVA-COD@Fe)exhibiting dual enzymatic activity was developed through a biomimetic mineralization approach.Cholesterol oxidase(COD)facilitated the consumption of cholesterol,thereby impairing the migratory capacity of tumor cells and diminishing resilience on oxidative stress.Concurrently,COD catalyzed the production of hydrogen peroxide(H2O2),which compensated for inadequate levels of tumor cells,thereby enhancing ferroptosis and ultimately inhibiting tumor growth and metastasis.Meanwhile,as an immune sensitizer,avasimibe altered cholesterol distribution,and promoted the infiltration and vitality of cytotoxic T lymphocytes into tumors jointly with immunogenic cell death(ICD)induced by ferroptosis,and enhanced anti-tumor immunity.To elicit significant immune memory effects,this nanosystem was further combined with the anti-programmed cell death protein ligand-1 antibody,which effectively inhibited the growth of both primary and metastatic tumors,and demonstrated a robust systemic anti-tumor immune response.This study addressed modulation of tumor cell cholesterol metabolism as a strategic entry point for tumor suppression,significantly curtailing tumor progression,and activating systemic immune responses,thereby offering a new perspective for future cancer therapies.展开更多
文摘Abnormal activation of the Ras/Raf/Mek/Erk signaling cascade plays an important role in glioma. Inhibition of this aberrant activity could effectively hinder glioma cell proliferation and promote cell apoptosis. To investigate the mechanism of gJioblastoma treatment by neural stem ceiJ trans- plantation with respect to the Ras/Raf/Mek/Erk pathway, C6 glioma cells were prepared in sus- pension and then infused into the rat brain to establish a glioblastoma model. Neural stem cells isolated from fetal rats were then injected into the brain of this glioblastoma model. Results showed that Raf-1, Erk and Bcl-2 protein expression significantly increased, while Caspase-3 protein expression decreased. After transplantation of neural stem cells, Raf-1, Erk and Bcl-2 protein expression significantly decreased, while Caspase-3 protein expression significantly in-creased. Our findings indicate that transplantation of neural stem cells may promote apoptosis of glioma cells by inhibiting Ras/Raf/Mek/Erk signaling, and thus may represent a novel treatment approach for glioblastoma.
基金supported by the National Natural Science Foundation of China(No.32571629)the Natural Science Foundation of Liaoning Province(Nos.2024011874-JH4/4800,2023-MS-198,and 2023011989-JH3/4600)+1 种基金Scientific Research Projects of Liaoning Provincial Department of Education(Nos.LJ212410163004 and LJKMZ20221786)Career Development Support Program for Young and Middle-aged Teachers(No:ZQN202208)of Shenyang Pharmaceutical University.
文摘The occurrence and development of cancer are closely related to dysregulation of cholesterol metabolism.Therefore,targeting cholesterol metabolism presents a novel diagnosis and treatment strategy for cancer.In this study,a nanosystem(AVA-COD@Fe)exhibiting dual enzymatic activity was developed through a biomimetic mineralization approach.Cholesterol oxidase(COD)facilitated the consumption of cholesterol,thereby impairing the migratory capacity of tumor cells and diminishing resilience on oxidative stress.Concurrently,COD catalyzed the production of hydrogen peroxide(H2O2),which compensated for inadequate levels of tumor cells,thereby enhancing ferroptosis and ultimately inhibiting tumor growth and metastasis.Meanwhile,as an immune sensitizer,avasimibe altered cholesterol distribution,and promoted the infiltration and vitality of cytotoxic T lymphocytes into tumors jointly with immunogenic cell death(ICD)induced by ferroptosis,and enhanced anti-tumor immunity.To elicit significant immune memory effects,this nanosystem was further combined with the anti-programmed cell death protein ligand-1 antibody,which effectively inhibited the growth of both primary and metastatic tumors,and demonstrated a robust systemic anti-tumor immune response.This study addressed modulation of tumor cell cholesterol metabolism as a strategic entry point for tumor suppression,significantly curtailing tumor progression,and activating systemic immune responses,thereby offering a new perspective for future cancer therapies.
