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Archive > Volume 28 Issue 9 > 2021,28(9):877-884. DOI:10.3872/j.issn.1007-385X.2021.09.003 Prev Next
Basic Research
Formononetin affects the pathogenesis of liver cancer by inhibiting the COX-2/ cyclin D1 axis
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Abstract:
Objective: To analyze the relationship between the expression of cyclooxygenase-2 (COX-2) and clinicopathological features and prognosis of patients with liver cancer, and to explore the role and mechanism of formononetin (FOR) in the pathogenesis of liver cancer. Methods: The clinical data of 60 patients with liver cancer and 20 pairs of surgically resected cancer tissues and corresponding para-cancerous tissues from liver cancer patients that treated in the Fourth Hospital of Hebei Medical University during January 2021 and May 2021 were collected for this study; in addition, human liver cancer cell lines HepG2 and Bel-7402 were also collected. The expression of COX-2 in liver cancer tissues was detected by qPCR and immunohistochemical staining, and the relationship between COX-2 expression and clinicopathological characteristics and prognosis of patients was analyzed. Diethylnitrosamine-induced mouse model of liver cancer was established to verify the effect of FOR on the incidence of liver cancer. After being treated with 0.003 and 0.006 μmol/ml FOR 48 h, the effects of FOR on proliferation and cell cycle of HepG2 and Bel-7402 cells were detected by CCK-8 and Flow cytometry. The changes in the expression of COX-2, CDK4, CDK6 and cyclin D1 were detected by qPCR and WB. Results: The mRNA expression of COX-2 in liver cancer tissues was significantly higher than that in para cancerous tissues ( P<0.01 ). The positive expression rate of COX-2 in liver cancer tissues was 68.3% (41/60), and the positive expression of COX-2 was correlated with advanced TNM stage, large tumor and short survival (all P<0.05 ). In the xenograft mouse model of induced liver cancer, the incidence of liver cancer in mice treated with FOR was significantly reduced, and the expression of COX-2 in liver tissues was significantly decreased (all P<0.05 ). FOR significantly inhibited the proliferation, increased the proportion of cells at G0/G1 phase, decreased the proportion of cells at S and G2 phase (all P<0.05 ), and inhibited the expression of COX-2 and cyclin D1 in HepG2 and Bel-7402 cells (all P<0.01 ). Conclusion: Liver cancer patients with positive COX-2 expression have an advanced clinical stage and a poor prognosis. FOR can prevent the occurrence and development of liver cancer by inhibiting the expression of COX-2 and cyclin D1.
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Project Supported:
Project supported by the Research Foundation from Bureau of Health of Hebei Province (No. 20200110)
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