| External factors: | Palbociclib |
| Aging type: | Accelerate |
| Aging characteristic: |
| Category: | Chemical compounds |
| Phenotype: | Malignant pleural mesothelioma |
| Experiment: | Cell cycle analysis//Cell morphological analysis//SA-β-gal activity assay//Western blot |
| Description: | Palbociclib induced a significant blockade of the progression from G1 to S phase of the cell cycle in all MPM sensitive cells; Interestingly, treatment with palbociclib induced an accumulation of senescent-like cells, characterized by the production of the Senescent-Associated β-galactosidase enzyme (SA-β-Gal) and by flat and enlarged cell morphology;In addition, the level of cyclin D1 was increased, confirming cyclin D1 induction as a marker associated to cellular senescence. |
| Target gene: | P21 |
| R-EF-Target gene: | Upregulation |
| Official symbol(s): | P21 |
| Target gene experiment: | Western blot |
| Target gene description: | We observed a great increase in p21 expression,that might be ascribed to the release of p21 gene negative regulation exerted by myc, or to AKT/mTOR signaling activation, which has been shown to initiate p21-dependent senescence in particular conditions. |
| Regulatory pathway: | Akt-mTOR |
| R-EF-Pathway: | Activation |
| Official symbol(s): | AKT1-MTOR |
| Pathway experiment: | Western blot |
| Pathway description: | The additive/synergistic inhibitory effects of the drug combination on cell proliferation were associated with a significant downregulation of p-CDK6, p-Rb, Rb levels, as well as with the inhibition of the AKT/mTOR pathway in both MSTO and ZS-LP cells. |
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