[Effect and mechanism of Modified Qinghao Biejia Decoction medicated serum in inducing ferroptosis in acute myeloid leukemia cells based on TFR1/ACSL4/LPCAT3 signaling axis].

To investigate the effect and underlying mechanism of Modified Qinghao Biejia Decoction(MQHBJD) medicated serum in inducing ferroptosis in acute myeloid leukemia(AML) cells, New Zealand rabbits were administered by intragastric gavage to prepare MQHBJD-containing serum and blank serum. After determining the experimental concentrations and incubation time of MQHBJD and the ferroptosis inhibitor Fer-1 by CCK-8 assay, MOLM-13 cells were divided into five groups: blank, 2.5% MQHBJD-containing serum, 5% MQHBJD-containing serum, 10% MQHBJD-containing serum, and 5% MQHBJD-containing serum + Fer-1. Related indicators were detected after 24 hours of intervention. The results showed that, compared with the blank group, the cell inhibition rates in all MQHBJD-containing serum groups were significantly higher(P<0.05, P<0.01, P<0.001), with the 10% MQHBJD-containing serum group exhibiting the highest rate, however, there was no significant difference between this group and the 5% MQHBJD-containing serum group. Levels of malondialdehyde(MDA) and ferrous ions(Fe~(2+)) in the cell culture supernatant were significantly elevated(P<0.05, P<0.01, P<0.001), while glutathione(GSH) levels were significantly decreased(P<0.001); the fluorescence area of reactive oxygen species(ROS) gradually increased(P<0.001), mitochondria exhibited marked atrophy and a reduction in cristae, and ferritin heavy chain 1(FTH1) mRNA and protein expression were significantly decreased(P<0.05, P<0.01, P<0.001), while transferrin receptor 1(TFR1), acyl-CoA synthase long-chain family member 4(ACSL4), and lysosomal phosphatidylcholine acyltransferase 3(LPCAT3) mRNA and protein expression significantly increased(P<0.05, P<0.01, P<0.001). Compared with the 5% MQHBJD-containing serum group, the cell inhibition rate was significantly lower in the 5% MQHBJD-containing serum + Fer-1 group(P<0.001), MDA and Fe~(2+) levels were significantly reduced(P<0.05, P<0.001), GSH levels were significantly increased(P<0.01), the ROS fluorescence area was significantly decreased(P<0.001), mitochondrial atrophy and reduced cristae were improved, FTH1 protein expression was significantly increased(P<0.01), and TFR1, ACSL4, LPCAT3 protein expression were significantly decreased(P<0.001). In conclusion, MQHBJD can effectively induce ferroptosis in AML cells, and its mechanism may be related to the regulation of the TFR1/ACSL4/LPCAT3 signaling axis.