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

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 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 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.