Downregulation of PTEN mediates bleomycin-induced premature senescence in lung cancer cells by suppressing autophagy

• Published in: Journal of international medical research Vol. 48; no. 5; p. 300060520923522
• Main Authors: Sai, Xiaoyan, Qin, Chu, Wu, Yan, Zhao, Yinying, Bian, Tao
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.05.2020; Sage Publications Ltd; SAGE Publishing
• Subjects: A549 Cells; Autophagy; Autophagy - drug effects; Bleomycin - pharmacology; Bleomycin - therapeutic use; Cellular Senescence - drug effects; Chemotherapy; Down-Regulation - drug effects; Gene Expression Regulation, Neoplastic - drug effects; Humans; Kinases; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - metabolism; PTEN Phosphohydrolase - metabolism; Senescence; Signal Transduction - drug effects; TOR Serine-Threonine Kinases - metabolism; Validation Study; PTEN; bleomycin; cancer cell; autophagy; PI3K/Akt/mTOR pathway; premature senescence
• ISSN: 0300-0605; 1473-2300; 1473-2300
• DOI: 10.1177/0300060520923522

Objective 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. Methods 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 PTEN 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. Results 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 PTEN reduced autophagy and accelerated senescence of A549 cells. Autophagy levels were also increased and senescence markers were reduced after inhibiting mTOR. Conclusions 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.