Journal of Shandong University (Health Sciences) ›› 2022, Vol. 60 ›› Issue (10): 9-16.doi: 10.6040/j.issn.1671-7554.0.2022.0282

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Effects and mechanism of interfering MAD2L1 gene expression on the apoptosis of breast cancer cells

FENG Haigang1, LIU Guowen2, CAO Hong1   

  1. 1. Department of Thyroid and Breast Surgery, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China;
    2. Department of Thyroid and Breast Surgery, Shenzhen Second Peoples Hospital, Shenzhen 518025, Guangdong, China
  • Published:2022-09-30

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Abstract: Objective To explore the effects of interference with mitotic arrest deficient 2-like protein 1(MAD2L1)gene expression on breast cancer(BC)cell apoptosis and the mechanism. Methods The mRNA expressions of MAD2L1 in normal breast epithelial cell line MCF-10A and BC cell lines, including MDA-MB-231, MCF-7, SK-BR-3 and BT-20, were detected with qRT-PCR. After MAD2L1 siRNA was transfected into MDA-MB-231 cells, the mRNA and protein expressions of MAD2L1 were detected with qRT-PCR and Western blotting; cell proliferation ability was measured with MTT; cell apoptosis was detected with Annexin V-FITC/PI; expressions of Bax, Bcl-2, cleaved-caspase-3, p-p38MAPK(Thr180/Thr182)and p38MAPK were determined with Western blotting. After the above cells were treated with the p38MAPK inhibitor SB203580 in combination, the changes in apoptosis rate were detected with flow cytometry, and changes in the expressions of Bax, Bcl-2, cleaved-caspase-3, p-p38MAPK and p38MAPK were detected with Western blotting. Results The mRNA expression of MAD2L1 in BC cell line, especially in MDA-MB-231 cells, was significantly higher than that in MCF-10A cells. Interference with MAD2L1 gene reduced the mRNA and protein expressions of MAD2L1 in MDA-MB-231 cells(tmRNA=10.51, PmRNA<0.001; tprotein=18.30, Pprotein<0.001), inhibited cell proliferation(Fgroup=243.36, Ftime=44.00, Fgroup × time=9.881, all P<0.001), promoted cell apoptosis(t=9.10, P<0.001), up-regulated the protein expressions of Bax, cleaved-caspase-3 and p-p38MAPK(tBax=15.05, PBax<0.001; tcleaved-caspase-3=5.26, Pcleaved-caspase-3=0.006; tp-p38MAPK=28.46, Pp-p38MAPK<0.001), and down-regulated the protein expression of Bcl-2(tBcl-2=14.23, PBcl-2<0.001). However, SB203580 treatment inhibited the induction of apoptosis by MAD2L1 gene interference on MDA-MB-231 cells(P=0.002). Conclusion Interfering with the expression of MAD2L1 gene can inhibit the proliferation of MDA-MB-231 cells and induce apoptosis, and the mechanism may be related to the activation of the p38MAPK signaling pathway.

Key words: Breast cancer, Mitotic arrest defect 2-like protein 1, Apoptosis, p38MAPK signaling pathway

CLC Number: 

  • R737.9
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