AS1411对耐紫杉醇肺腺癌A549细胞凋亡的影响

[Effects of AS1411 on the apoptosis of taxol-resistant lung adenocarcinoma A549 cell].

作者信息

Zhou Wei, Zhao Zitong, Liu Lingyan, Zhan Qimin, Song Yongmei

机构信息

State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.

State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. Email:

出版信息

Zhonghua Yi Xue Za Zhi. 2014 May 13;94(18):1422-6.

PMID:25142997

Abstract

OBJECTIVE

To explore the effects of AS1411 on the apoptosis of taxol-resistant lung adenocarinoma A549 cell (A549/T cell).

METHODS

A549/T cells were treated with AS1411 at a concentration gradient of 0-20.0 µmol/L. The assays of methyl tolyl sulfide (MTS) and colony formation were used to detect the cellular vitality (absorbance value (A490 nm)) and proliferation. The apoptotic effects were detected by flow cytometer and the relevant apoptotic signaling proteins detected by Western blot.

RESULTS

A549/T cells exhibited some characteristics of epithelial mesenchymal transition (EMT) and a negative expression of epidermal growth factor receptor (EGFR). After a treatment of 5.0 µmol/L AS1411, compared to the control sequence, cell vitality was inhibited (A490 nm: 0.185 ± 0.009 vs 0.272 ± 0.006, P < 0.001) and the number of clone formation decreased (74 ± 13 vs 120 ± 12, P = 0.010). With rising AS1411 concentration, A549/T cells vitality decreased in a dose-dependent manner. After a 48-hour treatment of 20.0 µmol/L AS1411, the ratio of apoptosis ((19.9 ± 2.6)%) had significant difference (P = 0.002) with the control sequence group ((8.8 ± 1.3)%). Compared to the control sequence group, the expressions of protein kinase B (AKT), extracellular regulated protein kinases 1/2 (ERK1/2) and B-cell lymphoma 2 (Bcl-2) protein declined (0.353 ± 0.003, 0.432 ± 0.015, 0.294 ± 0.015 vs 0.688 ± 0.003, 0.911 ± 0.019, 0.422 ± 0.018, all P < 0.001).

CONCLUSION

AS1411 may induce the apoptosis of A549/T cells through inhibiting the AKT-ERK pathways.

摘要

目的

探讨AS1411对耐紫杉醇肺腺癌A549细胞（A549/T细胞）凋亡的影响。

方法

用浓度为0～20.0μmol/L的AS1411处理A549/T细胞。采用甲基甲苯基硫醚（MTS）法和集落形成实验检测细胞活力（吸光度值（A490nm））和增殖情况。用流式细胞仪检测凋亡效应，用蛋白质免疫印迹法检测相关凋亡信号蛋白。

结果

A549/T细胞表现出一些上皮-间质转化（EMT）特征，且表皮生长因子受体（EGFR）呈阴性表达。用5.0μmol/L AS1411处理后，与对照序列相比，细胞活力受到抑制（A490nm：0.185±0.009比0.272±0.006，P<0.001），集落形成数量减少（74±13比120±12，P=0.010）。随着AS1411浓度升高，A549/T细胞活力呈剂量依赖性下降。用20.0μmol/L AS1411处理48小时后，凋亡率（（19.9±2.6）%）与对照序列组（（8.8±1.3）%）相比有显著差异（P=0.002）。与对照序列组相比，蛋白激酶B（AKT）、细胞外调节蛋白激酶1/2（ERK1/2）和B细胞淋巴瘤2（Bcl-2）蛋白的表达下降（0.353±0.003、0.432±0.015、0.294±0.015比0.688±0.003、0.911±0.019、0.422±0.018，均P<0.001）。