Long-Term Effects of Sirolimus on Human Skin TSC2-Null Fibroblast‒Like Cells

This study investigated the effects of sirolimus on TSC2-null fibroblast-like cells derived from tuberous sclerosis complex (TSC) skin tumors. Sirolimus was found to reduce the size and proliferation of TSC2−/− cells by modulating the mTOR pathway, specifically affecting cell cycle progression and autophagy. The study demonstrated that sirolimus decreased the volume of TSC2−/− cells but not TSC2+/− cells, indicating a selective effect on tumor cells. Withdrawal of sirolimus led to increased proliferation and cell cycle re-entry in TSC2−/− cells, highlighting the need for continuous treatment to maintain its therapeutic benefits. These findings suggested that sirolimus could potentially be used to manage TSC-related tumors by targeting specific cellular pathways. Additionally, the study explored the effects of estrogen and chloroquine, finding that estrogen increased cell volume in TSC2−/− cells, while chloroquine increased TSC2+/− cell volume but not TSC2−/− cells. The combination of sirolimus and chloroquine showed synergistic effects in reducing cell volume, suggesting that sirolimus therapy might need to be combined with other drugs to prevent regrowth of tumors and decline in lung function.