[Autophagy Regulates the Sensitivity of Acute Lymphoblastic Leukemia Cells to Ferroptosis Activator by Influencing Iron Homeostasis].

OBJECTIVE

To investigate the effect of autophagy to the ferroptosis in acute lymphocytic leukemia (ALL) cells and its mechanism.

METHODS

ALL cell lines (including Reh, Jurkat and CCRF-CEM) were selected. The cell viability was detected by MTS assay and trypan blue staining was used to evaluate the death of the cell. The expression of autophagy related protein (including p62, LC3I/II) and Ferritin in ALL cells were detected by Western blot. The alteration of labile iron pool (LIP) in ALL cells was evaluated by flow cytometry.

RESULTS

Reh cells showed sensitivity to ferroptosis activator Erastin, while Jurkat and CCRF-CEM cells showed resistant. Autophagy activator rapamycin could promote the sensitivity of Jurkat and CCRF-CEM cells to Erastin, and the ferroptosis of the cells (P<0.001). Autophagy inhibitor chloroquine could reduce the sensitivity of Reh cells to Erastin and resist the ferroptosis of the cells (P<0.001). The expression of Ferritin could be down-regulated after autophagy was activated in Jurkat and CCRF-CEM cells (P<0.05), while the level of LIP was significantly increased (P<0.05). Inhibiting the autophgy in Reh cells could up-regulate the expression of Ferritin (P<0.01),while decrease the level of LIP (P<0.001).

CONCLUSION

The iron homeostasis in cells could be regulated by autophagy through affecting Ferritin expression and LIP level. Autophagy can alter sensitivity of ALL cells to ferroptosis activator Erastin, which suggestes that combining autophagy regulator with ferroptosis activator may be a new strategy for the treatment of chemotherapy-resistant ALL.