Cabazitaxel-induced autophagy via the PI3K/Akt/mTOR pathway contributes to A549 cell death.
Cabazitaxel-induced autophagy via the PI3K/Akt/mTOR pathway contributes to A549 cell death.
复制标题
卡巴他赛通过 PI3K/Akt/mTOR 途径诱导的自噬导致 A549 细胞死亡
DOI：
10.3892/mmr.2016.5648
复制
发表时间：
2016-10
影响因子：
3.4
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Huo R;Wang L;Liu P;Zhao Y;Zhang C;Bai B;Liu X;Shi C;Wei S;Zhang H
卡巴他赛自2010年被美国食品和药物管理局批准以来一直用于治疗去势抵抗性前列腺癌。然而，卡巴他赛是否可以抑制其他组织来源的癌细胞的增殖及其潜在机制仍然未知。在本研究中，将A549肺腺癌细胞系暴露于卡巴他赛，以研究其细胞毒性作用并确定其潜在机制。结果表明卡巴他赛能够诱导A549细胞中的自噬，如通过自噬体的形成、上调LC 3-II表达和增加LC 3斑点所证明的。卡巴他赛诱导的自噬对A549细胞具有细胞毒性作用，表现为诱导细胞死亡和细胞周期停滞在G2/M期，这与凋亡途径无关。此外，用Beclin 1小干扰RNA转染和用自噬抑制剂3-甲基腺嘌呤处理保护细胞免于卡巴他赛诱导的细胞死亡，从而证实卡巴他赛诱导的自噬有助于A549细胞死亡。此外，卡巴他赛靶向磷酸肌醇3-激酶（PI 3 K）/Akt/哺乳动物雷帕霉素靶蛋白（mTOR）通路，以诱导自噬，如Akt和mTOR磷酸化减少所示。总之，本研究表明卡巴他赛通过作用于PI 3 K/Akt/mTOR通路促进自噬细胞死亡而对A549细胞产生细胞毒性作用。该结果支持卡巴他赛作为化疗剂用于治疗肺癌的潜在用途。
Cabazitaxel has been used to treat castration-resistant prostate cancer since its approval by the US Food and Drug Administration in 2010. However, whether cabazitaxel may inhibit the proliferation of other tissue-derived cancer cells, and its underlying mechanism, remains unknown. In the present study, the A549 lung adenocarcinoma cancer cell line was exposed to cabazitaxel, in order to investigate its cytotoxic effect and determine the underlying mechanism. The results demonstrated that cabazitaxel was able to induce autophagy in A549 cells, as evidenced by the formation of autophagosomes, upregulated LC3-II expression and increased LC3 puncta. Cabazitaxel-induced autophagy had a cytotoxic effect on A549 cells, as evidenced by the induction of cell death and cell cycle arrest at G2/M phase, which was independent of the apoptotic pathway. Furthermore, transfection with Beclin1 small interfering RNA and treatment with the autophagy inhibitor 3-methyladenine protected cells from cabazitaxel-induced cell death, thus confirming that cabazitaxel-induced autophagy contributed to A549 cell death. In addition, cabazitaxel targeted the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway to induce autophagy, as indicated by reduced phosphorylation of Akt and mTOR. In conclusion, the present study demonstrated that cabazitaxel exerts a cytotoxic effect on A549 cells by acting on the PI3K/Akt/mTOR pathway to promote autophagic cell death. This result supports the potential use of cabazitaxel as a chemotherapeutic agent for the treatment of lung cancer.
登录
查看更多内容
影响因子：
7.5
作者：
Deretic V
通讯作者：
Deretic V
影响因子：
3
作者：
Torrisi, Rosalba;Balduzzi, Alessandra;Colleoni, Marco
通讯作者：
Colleoni, Marco
影响因子：
5.1
作者：
Janda, Elzbieta;Isidoro, Ciro;Mollace, Vincenzo
通讯作者：
Mollace, Vincenzo
DOI：
10.1016/j.bbadis.2014.04.029
发表时间：
2015-02
影响因子：
6.2
作者：
Ren, Sidney Y.;Xu, Xihui
通讯作者：
Xu, Xihui
影响因子：
5.6
作者：
Sharma K;Le N;Alotaibi M;Gewirtz DA
通讯作者：
Gewirtz DA