Department of Respiratory Medicine, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, P.R. China.
J Int Med Res. 2020 May;48(5):300060520923522. doi: 10.1177/0300060520923522.
Bleomycin is an important chemotherapeutic drug that activates premature senescence to decrease the tumorigenic process. We aimed to investigate the role of phosphatase and tensin homolog deleted on chromosome ten (PTEN) in bleomycin-induced premature senescence in lung cancer cells.
Human lung cancer A549 cells were incubated in the presence of different concentrations of bleomycin for 5 days. A lentivirus vector was used to silence the gene, followed by stimulation with bleomycin (1 µg/mL). Changes were evaluated by senescence-associated β-galactosidase staining, reverse transcription-polymerase chain reaction, and western blot.
Treatment with bleomycin induced premature senescence. PTEN expression was decreased and key downstream molecules in the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway were gradually activated following bleomycin treatment. Silencing reduced autophagy and accelerated senescence of A549 cells. Autophagy levels were also increased and senescence markers were reduced after inhibiting mTOR.
Downregulation of PTEN mediates bleomycin-induced premature senescence in lung cancer cells by suppressing autophagy via the PI3K/Akt/mTOR pathway. These findings provide new insights into the potential role of PTEN as a molecular target for cancer chemotherapy.
博莱霉素是一种重要的化疗药物，可通过激活过早衰老来减少肿瘤发生过程。我们旨在研究抑癌基因磷酸酶张力蛋白同源物缺失（PTEN）在博莱霉素诱导肺癌细胞过早衰老中的作用。
将人肺癌 A549 细胞在不同浓度博莱霉素存在下孵育 5 天。使用慢病毒载体沉默 基因，然后用博莱霉素（1μg/ml）刺激。通过衰老相关β-半乳糖苷酶染色、逆转录-聚合酶链反应和 Western blot 评估变化。
博莱霉素处理诱导过早衰老。PTEN 表达降低，博莱霉素处理后磷酸肌醇 3-激酶（PI3K）/Akt/雷帕霉素靶蛋白（mTOR）通路的关键下游分子逐渐激活。沉默 基因减少自噬并加速 A549 细胞衰老。抑制 mTOR 后自噬水平增加，衰老标志物减少。
下调 PTEN 通过 PI3K/Akt/mTOR 通路抑制自噬介导博莱霉素诱导的肺癌细胞过早衰老。这些发现为 PTEN 作为癌症化疗的分子靶点提供了新的见解。
