Arsenic Inhibits Proliferation and Induces Autophagy of Tumor Cells in Pleural Effusion of Patients with Non-Small Cell Lung Cancer Expressing EGFR with or without Mutations via PI3K/AKT/mTOR Pathway.
Arsenic Inhibits Proliferation and Induces Autophagy of Tumor Cells in Pleural Effusion of Patients with Non-Small Cell Lung Cancer Expressing EGFR with or without Mutations via PI3K/AKT/mTOR Pathway.
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DOI：
10.3390/biomedicines11061721
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发表时间：
2023-06-15
期刊：
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
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作者：
为明确砷是否能对非小细胞肺癌（NSCLC）患者胸腔积液中的肿瘤细胞产生抑制作用，于2019年至2022年在长征医院和瑞金医院采集了36例NSCLC胸腔积液样本。鉴定表皮生长因子受体（EGFR）基因型。分离肿瘤细胞并用三氧化二砷（ATO）或/和吉非替尼处理。此外，6例患者胸腔内给予ATO。结果显示，25例样本携带EGFR野生型（WT），11例携带EGFR突变，包括6例携带L 858 R，3例携带ΔE746-A750，2例携带T790 M。ATO减少了WT和突变型EGFR患者的肿瘤细胞数量，下调了EGFR、pmTOR、PI 3 K、PTEN和p4 E-BP 1的表达或磷酸化，并上调了LC 3的表达。免疫荧光实验显示ATO可增强LC 3和P62。相比之下，吉非替尼仅对携带EGFR致敏突变的患者有效。值得注意的是，在胸腔内注射ATO的患者中，胸腔积液经历了血性至浅黄色的颜色变化，胸腔积液的体积减少，并且肿瘤细胞的数量显著减少。总之，砷在体外和体内对不同EGFR基因型的NSCLC有效，并可能避免吉非替尼耐药。
To clarify whether arsenic could exert inhibitory effects on tumor cells in pleural effusions of patients with non-small cell lung cancer (NSCLC), 36 NSCLC pleural effusion samples were collected from Changzheng Hospital and Ruijin Hospital, from 2019 to 2022. The genotype of epidermal growth factor receptor (EGFR) was identified. Tumor cells were isolated and treated with arsenic trioxide (ATO) or/and gefitinib. Additionally, six patients were intrapleurally administrated with ATO. Results showed that 25 samples bore EGFR wild type (WT) and 11 harbored EGFR mutations, including 6 with L858R, 3 with ΔE746-A750, and 2 with T790M. ATO diminished the number of tumor cells from patients with WT and mutant EGFR, down-regulated the expression or phosphorylation of EGFR, pmTOR, PI3K, PTEN, and p4E-BP1, and up-regulated the expression of LC3. Immunofluorescent experiments showed that ATO enhanced LC3 and P62. By contrast, gefitinib was only effective in those harboring EGFR sensitizing mutations. Notably, in patients with intrapleural ATO injection, the pleural effusion underwent a bloody to pale yellow color change, the volume of the pleural effusion was reduced, and the number of the tumor cells was significantly reduced. In conclusion, arsenic is effective against NSCLC with various EGFR genotypes in vitro and in vivo, and potentially circumvents gefitinib resistance.
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恶性胸腔积液中多种免疫表型的单细胞分析
影响因子：
16.6
作者：
Huang ZY;Shao MM;Zhang JC;Yi FS;Du J;Zhou Q;Wu FY;Li S;Li W;Huang XZ;Zhai K;Shi HZ
通讯作者：
Shi HZ
DOI：
10.1158/1078-0432.ccr-18-1542
发表时间：
2018-12-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Le X;Puri S;Negrao MV;Nilsson MB;Robichaux J;Boyle T;Hicks JK;Lovinger KL;Roarty E;Rinsurongkawong W;Tang M;Sun H;Elamin Y;Lacerda LC;Lewis J;Roth JA;Swisher SG;Lee JJ;William WN Jr;Glisson BS;Zhang J;Papadimitrakopoulou VA;Gray JE;Heymach JV
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Heymach JV
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DOI：
10.1073/pnas.0813280106
发表时间：
2009-03-03
影响因子：
11.1
作者：
Hu, Jiong;Liu, Yuan-Fang;Chen, Zhu
通讯作者：
Chen, Zhu
影响因子：
8
作者：
Gong L;Zhang Y;Liu C;Zhang M;Han S
通讯作者：
Han S
影响因子：
5.6
作者：
Kryczka J;Kryczka J;Czarnecka-Chrebelska KH;Brzeziańska-Lasota E
通讯作者：
Brzeziańska-Lasota E