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L‐Se‐methylselenocysteine sensitizes lung carcinoma to chemotherapy
Authors:Jia Ma  Jing Huang  Jinli Sun  Yanfeng Zhou  Xiaoyuan Ji  Daoxia Guo  Chang Liu  Jiyu Li  Jiye Zhang  Haiyun Song
Institution:1. School of Pharmacy, Health Science Center, Xi''an Jiaotong University, Xi''an China ; 2. State Key Laboratory of Oncogenes and Related Genes, Center for Single‐Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai China ; 3. Department of Neurology, Xuhui District Central Hospital, Shanghai China ; 4. Henan Xibaikang Health Industry Co., Ltd, Jiyuan China
Abstract:ObjectivesOrganic Selenium (Se) compounds such as L‐Se‐methylselenocysteine (L‐SeMC/SeMC) have been employed as a class of anti‐oxidant to protect normal tissues and organs from chemotherapy‐induced systemic toxicity. However, their comprehensive effects on cancer cell proliferation and tumour progression remain elusive.Materials and MethodsCCK‐8 assays were conducted to determine the viabilities of cancer cells after exposure to SeMC, chemotherapeutics or combined treatment. Intracellular reactive oxygen species (ROS) levels and lipid peroxidation levels were assessed via fluorescence staining. The efficacy of free drugs or drug‐loaded hydrogel against tumour growth was evaluated in a xenograft mouse model.ResultsAmong tested cancer cells and normal cells, the A549 lung adenocarcinoma cells showed higher sensitivity to SeMC exposure. In addition, combined treatments with several types of chemotherapeutics induced synergistic lethality. SeMC promoted lipid peroxidation in A549 cells and thereby increased ROS generation. Significantly, the in vivo efficacy of combination therapy was largely potentiated by hydrogel‐mediate drug delivery.ConclusionsOur study reveals the selectivity of SeMC in the inhibition of cancer cell proliferation and develops an efficient strategy for local combination therapy.
Keywords:chemotherapy  lipid peroxidation  lung carcinoma  methylselenocysteine
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