[Mechanism of lithium chloride-induced proliferation inhibition and apoptosis of K562 leukemic cells].
To investigate the mechanism of proliferation inhibition and apoptosis of K562 leukemia cells by lithium chloride (LiCl), after K562 cells were treated with LiCl (30 mmol/L) cell cycle was examined by flow cytometry (FCM) and the expression of bcr/abl fusion gene mRNA was evaluated by RT-PCR. The intracellular Li(+) concentrations of K562 cells were determined at different time after treated with 30 mmol/L LiCl and the effects of TTX and FSK on intracellular Li(+) concentrations of K562 cells were also detected by atomic absorption spectrometry. The effects of TTX and FSK on LiCl-induced growth inhibition of K562 cells were determined by cell counting in liquid culture. The results showed that LiCl (30 mmol/L) caused a sustained arrest in G(2)/M cell cycle and down-regulated the bcr/abl mRNA expression in K562 cells, the intracellular Li(+) concentration of K562 cells increased at 30 minutes after treated with 30 mmol/L LiCl and reached apex at 2 hours, thereafter, gradually decreased and balanced at 4 hours after the treatment. If either Na(+) channel was pre-blocked with TTX or K(+) channel was pre-blocked with FSK, the intracellular Li(+) concentrations of K562 cells treated with 30 mmol/L LiCl were higher than that in the cells just treated with LiCl without pre-blocking. Furthermore, after pre-blocking either Na(+) channel with TTX or K(+) channel with FSK, the inhibition rate of K562 cell growth by 30 mmol/L LiCl could be increased. It is concluded that the mechanism of proliferation inhibition and apoptosis of K562 leukemia cells induced by LiCl is probably related with the G(2)/M cell cycle arrest, the bcr/abl mRNA expression down-regulation and the status of Na(+), K(+), or Li(+) ion channels on K562 leukemia cells.
Tang
Hua-Rong
HR
Centeral Laboratory, Affiliated People's Hospital, Jiangsu University, Zhenjiang 210002, China.
He
Qun
Q
Wang
Fa-Chun
FC
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D005576:Colforsin / Q000494:pharmacology; D005434:Flow Cytometry; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018021:Lithium Chloride / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D000970:Antineoplastic Agents; D026902:Potassium Channel Blockers; D012333:RNA, Messenger; D026941:Sodium Channel Blockers; D005576:Colforsin; D013779:Tetrodotoxin; D016044:Fusion Proteins, bcr-abl; D018021:Lithium Chloride