Secreted Heat Shock Protein 90α Attenuated the Effect of Anticancer Drugs in Small-Cell Lung Cancer Cells Through AKT/GSK3β/β-Catenin Signaling.
Secreted Heat Shock Protein 90α Attenuated the Effect of Anticancer Drugs in Small-Cell Lung Cancer Cells Through AKT/GSK3β/β-Catenin Signaling.
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DOI：
10.1177/1073274818804489
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发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Luo L
中科院分区：
文献类型：
--
作者：
Du Y;Wu J;Luo L
小细胞肺癌(SCLC)是进展型肺癌。小细胞肺癌患者预后较差，部分原因是耐药。因此，了解小细胞肺癌耐药的潜在机制对于改善临床疗效是必要的。采用酶联免疫吸附试验检测培养上清液中热休克蛋白90α(HSP90α)的浓度。用Western印迹法检测细胞内蛋白质水平。细胞株用碘化丙啶染色，肿瘤切片用末端脱氧核苷酸转移酶dUTP缺口末端标记法检测细胞凋亡。将多柔比星(DOX)注入培养的细胞系或腹腔注射于异种小鼠体内诱导细胞凋亡。在小细胞肺癌细胞系中，DOX或ABT-737均可增加细胞外HSP90α水平，从而降低细胞凋亡率。细胞外热休克蛋白90α激活AK株转化和β-连环蛋白信号，抑制糖原合成酶ββ信号转导。在异种移植小鼠模型中，细胞外热休克蛋白90α促进肿瘤生长并抑制肿瘤细胞的凋亡。热休克蛋白90α通过AKT/GSK3β/β-连环蛋白信号通路减弱抗癌药物在小细胞肺癌细胞中的作用。
Small-cell lung cancer (SCLC) represents the progressive form of lung cancer. Patients with SCLC have poor prognosis, partially due to drug resistance. Therefore, understanding the underlying mechanism for drug resistance in SCLC is needed to improve clinical outcomes. The concentrations of heat shock protein 90α (HSP90α) in medium were detected by enzyme-linked immunosorbent assay. The protein levels were detected by Western blot. Cell apoptosis was detected by propidium iodide staining in cell lines or terminal deoxynucleotidyl transferase dUTP nick end labeling staining in tumor sections. Doxorubicin (DOX) was administered into cultured cell lines or intraperitoneally injected into xenograft mouse to induce apoptosis. In SCLC cell lines, either DOX or ABT-737 increased extracellular HSP90α levels, which attenuated the percentage of apoptotic cells. Extracellular HSP90α activated Ak strain transforming (AKT) and β-catenin signaling and inhibited glycogen synthase kinase 3β (GSK3β) signaling. In the xenograft mouse model, extracellular HSP90α promoted tumor development and inhibited apoptosis of tumor cells. Heat shock protein 90α attenuates the efficacy of anticancer drugs in SCLC cells through AKT/GSK3β/β-catenin signaling.
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DOI：
10.2741/e249
发表时间：
2011-01-01
期刊：
Frontiers in bioscience (Elite edition)
影响因子：
--
作者：
Park, Kang-Seo;Kim, Dae-Seok;Kim, Soo-Youl
通讯作者：
Kim, Soo-Youl
AKT抑制剂MK-2206通过调节结直肠癌的AIF和EZRIN促进抗肿瘤活性和细胞死亡。
影响因子：
3.8
作者：
Agarwal E;Chaudhuri A;Leiphrakpam PD;Haferbier KL;Brattain MG;Chowdhury S
通讯作者：
Chowdhury S
影响因子：
8
作者：
通讯作者：
--
影响因子：
6.2
作者：
Byers LA;Rudin CM
通讯作者：
Rudin CM
影响因子：
254.7
作者：
Siegel, Rebecca L.;Miller, Kimberly D.;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin