Journal of Shandong University (Health Sciences) ›› 2021, Vol. 59 ›› Issue (10): 25-31.doi: 10.6040/j.issn.1671-7554.0.2021.0230

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Effects of Trametinib on PAX8 expression in ovarian cancer

WANG Zhengyang1, XIA Yan2, SHI Kaixuan3, TAO Kun4, WANG Xiaojie1,2   

  1. 1. Graduate School of Bengbu Medical College, Bengbu 233000, Anhui, China;
    2. Department of Gynecology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200092, China;
    3. State Key Laboratory of Oncogenes and Related Genes, Clinical Stem Cell Research Center, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China;
    4. Department of Pathology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200050, China
  • Published:2021-10-15

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Abstract: Objective To investigate the effects of Trametinib, a MEK inhibitor, on PAX8 expression in ovarian cancer. Methods The expression changes of related genes in ovarian cancer cells treated with Trametinib were detected with gene set enrichment analysis(GSEA). The effects of Trametinib on the protein and mRNA expressions of PAX8 in ovarian cancer cells were detected with Western blotting, immunofluorescence staining and real-time quantitative PCR. The effects of Trametinib on the proliferation of ovarian cancer cells was detected with crystal violet staining. The change of PAX8 expression and cell proliferation in KRAS mutant ovarian cancer cells transfected with si-ELK1-RNA were detected with Western blotting, real-time quantitative PCR and CCK8 experiment. Results GSEA showed that Trametinib inhibited KRAS and ELK1 genes in ovarian cancer cells(P<0.01). Real-time quantitative PCR showed that Trametinib inhibited PAX8 transcription in KRAS mutant ovarian cancer cells(P<0.001). Crystal violet staining showed that Trametinib reduced the proliferation of KRAS mutated ovarian cancer cells. Western blotting showed that Trametinib inhibited the expression of PAX8 and ELK1 genes in KRAS mutant ovarian cancer cells(P<0.001), and interference with ELK1 gene inhibited the expression of PAX8 gene in KRAS mutant ovarian cancer cells(P<0.001); The results of CCK8 showed that interfering with ELK1 gene expression inhibited the proliferation of KRAS mutant ovarian cancer cells(P<0.05). Conclusion Trametinib inhibits PAX8 expression and cell proliferation through ELK1 gene in KRAS mutant ovarian cancer.

Key words: Trametinib, Ovarian cancer, PAX8 protein, Cell proliferation, KRAS gene mutation

CLC Number: 

  • R737.31
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