JNK通路介导的铁死亡在三阴性乳腺癌细胞增殖及凋亡中的作用

doi:10.3969/j.issn.1004-616x.2023.05.002

Abstract

Abstract: OBJECTIVE: To study the role of the c-Jun N-terminal kinase (JNK) pathway-mediated ferroptosis in the proliferation and apoptosis of triple negative breast cancer (TNBC). METHODS: From January 2020 to May 2022,105 cases of TNBC tissues and adjacent tissues which were resected surgically in the First Affiliated Hospital of Jiamusi University were collected, TNBC cell line MDA-MB-231 and non TNBC cell lines MCF-7, SK-BR-3 were cultured. Expression levels of p-JNK and ferroptosis marker gene transferrin receptor 1 (TFR1) and glutathione peroxidase 4 (GPX4) in the tissues and the TNBC cells and non TNBC cells were detected. MDA-MB-231 cells in cultures were divided into the control and the JNK agonist groups (5 μmol/L ANISO),the ferroptosis inhibitor (2 μmol/L ferrostatin-1),and the agonist+inhibitor groups (5 μmol/L ANISO+2 μmol/L ferrostatin-1). After 24h treatment in each group, proliferation inhibition rates were detected using the CCK-8 assay,apoptosis rates by the TUNEL assay,activities of glutathione peroxidase (GSH),superoxide dismutase (SOD) and the content of malondialdehyde (MDA) were by kits,and expression levels of p-JNK, TFR1 and GPX4 were by PCR and western blot. RESULTS: Compared with adjacent tissues,expression levels of p-JNK and TFR1 in the TNBC tissues were decreased,but the levels for GPX4 were increased (P<0.05). p-JNK expressions were positively correlated with TFR1(correlation coefficient r=0.515,P<0.05) and negatively correlated with GPX4 (correlation coefficient r=-0.442,P<0.05). Compared with the MCF-7 and SK-BR-3 cells,expression levels of p-JNK and TFR1 in MDA-MB-231 were decreased,and expression levels of GPX4 were increased (P<0.05). Compared with the control group,proliferation inhibition rates,apoptosis rates,the expression levels of TFR4,and contents of MDA were increased (P<0.05),while expression levels of GPX4,and activities of GSH and SOD were decreased in the JNK agonist group (P<0.05). In addition,proliferation inhibition rates,apoptosis rates,activities of GSH and SOD,and contents of MDA showed no significant changes (P>0.05),while expression levels of TFR4 were decreased and expression levels of GPX4 were increased (P<0.05) in the ferroptosis inhibitor group. Compared with JNK agonist group, proliferation inhibition rates,apoptosis rates,expression levels of TFR4,contents of MDA were decreased (P<0.05), while expression levels of GPX4, and activities of GSH and SOD were increased in the agonist + inhibitor group (P<0.05). CONCLUSION: Activation of the JNK pathway inhibited proliferation and promoted apoptosis of TNBC cell by activating ferroptosis.

Key words: triple negative breast cancer, c?Jun N?terminal kinase, ferroptosis, proliferation, apoptosis

CLC Number:

R737.9

ZHANG Chenxin, ZHOU Yu. Role of JNK pathway mediated ferroptosis in proliferation and apoptosis of triple negative breast cancer cells[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2023, 35(5): 334-340.

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Role of JNK pathway mediated ferroptosis in proliferation and apoptosis of triple negative breast cancer cells

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