Dataset Information


GPX4-dependent Glutathione (GSH) high consumption drives platinum chemotherapeutic resistance by inhibiting ferroptosis in lung cancer derived brain metastasis

ABSTRACT: Platinum-based chemotherapy is effective in inducing shrinkage of primary lung cancer lesions; however, it shows limited therapeutic efficacy in patients with brain metastasis (BM). In this study, we utilized a BM model of PC9 lung adenocarcinoma cells and found that the derivative brain metastatic subpopulations (PC9-BrMs) of parental cells PC9 developed obvious resistance to platinum; this suggested that the acquisition of chemo-resistance by brain metastatic cells is attributable to the intrinsic changes in the metastatic cells. Therefore, we performed an integrated profiling of metabolomics and proteomics, and described a radically altered spectrum of BM metabolism and protein expression compared with primary lung cancer cells. We identified a unique metabolite status characterized by high consumption of glutathione (GSH) for antioxidant stress response, both in BM cells and clinical serum samples.

INSTRUMENT(S): quadrupole

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture



PROVIDER: PXD019638 | Pride | 2022-02-15


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Action DRS
L-B2-Br0-1.qgd Other
L-B2-Br0-2.qgd Other
L-B2-Br0-3.qgd Other
L-B2-Br0-5.qgd Other
L-B2-Br0-6.qgd Other
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Glutathione peroxidase 4-dependent glutathione high-consumption drives acquired platinum chemoresistance in lung cancer-derived brain metastasis.

Liu Wenwen W   Zhou Yang Y   Duan Wenzhe W   Song Jing J   Wei Song S   Xia Shengkai S   Wang Yingyan Y   Du Xiaohui X   Li Encheng E   Ren Caixia C   Wang Wei W   Zhan Qimin Q   Wang Qi Q  

Clinical and translational medicine 20210901 9

<h4>Background</h4>Platinum-based chemotherapy is effective in inducing shrinkage of primary lung cancer lesions; however, it shows finite therapeutic efficacy in patients suffering from brain metastasis (BM). The intrinsic changes of BM cells, which contribute to the poor results remain unknown.<h4>Methods</h4>Platinum drug-sensitivity was assessed by utilizing a preclinical BM model of PC9 lung adenocarcinoma cells in vitro and in vivo. High consumption of glutathione (GSH) and two associated  ...[more]

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