L‐Se‐methylselenocysteine sensitizes lung carcinoma to chemotherapy |
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Authors: | Jia Ma Jing Huang Jinli Sun Yanfeng Zhou Xiaoyuan Ji Daoxia Guo Chang Liu Jiyu Li Jiye Zhang Haiyun Song |
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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 |
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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. |
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Keywords: | chemotherapy lipid peroxidation lung carcinoma methylselenocysteine |
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