Rapamycin induces autophagy and apoptosis in Kaposiform hemangioendothelioma primary cells in vitro

Background: Rapamycin has been recommended to treat Kaposiform hemangioendothelioma (KHE) with Kasabach-Merritt phenomenon (KMP), but the underlying mechanism of the clinical effect has not been established. Therefore, we determined rapamycin cytotoxicity on KHE cells in vitro and the underlying mechanism. Methods: KHE primary cells were derived from a tumor specimen and treated with rapamycin. Immunofluorescence was applied to identify the cells. Cell viability was measured using the Cell Counting Kit-8 (CCK-8) assay. Cell cycle and apoptosis were assessed using flow cytometry (FCM). Western blots (WB) were performed to determine phosphorylation of mammalian target of rapamycin (mTOR), p70 S6 kinase (S6K1), and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), as well light chain 3 (LC3) expression. Results: Rapamycin inhibited the growth of KHE primary cells in a dose- and time-dependent manner. Cell cycle progression was arrested in the G0/G1 phase and apoptosis was induced. WB results showed that LC3-II/I expression was significantly elevated in KHE primary cells treated with rapamycin, while the level of p-mTOR, p-S6K1, and p-4E-BP1 expression was reduced. LC3 fluorescent spots were increased in the rapamycin treatment group. Conclusions: Rapamycin inhibited KHE primary cell proliferation, induced apoptosis and autophagy, and blocked the mTOR signaling pathway. (C) 2022 Elsevier Inc. All rights reserved.

Automated summary

This study found that rapamycin can inhibit the proliferation of KHE primary cells, induce apoptosis and autophagy by blocking the mTOR signaling pathway.