Authors

Shijun Wang#, Jiayu Wang, Lin Wang

Departments

Department of Otolaryngology, The First Hospital of Harbin, Harbin, PR China

Abstract

Objective: To explore the mechanism by which metformin inhibits hypopharyngeal cancer cell proliferation by regulating the expression of miR-21-5p and PDCD4. 

Methods: FaDu hypopharyngeal cancer cells were collected and passaged regularly. To investigate how metformin inhibits tumor growth, we measured cell proliferation, miR-21-5p and PDCD4 mRNA expression in the FaDu hypopharyngeal cancer cell line with and without different concentrations of metformin (25 mmol/L, 50 mmol/L, 75 mmol/L, 100 mmol/L). We dissected the role of miR-21-5p in FaDu cells using a miR-21-5p inhibitor. The effects of miR-21-5p inhibitors on PDCD4 expression were observed in the miRNA-21-5p inhibitor group and the normal control group (without treatment). 

Results: There was a significant difference in the cell inhibition rate among the different concentrations of metformin tested. Metformin concentrations of 50 mmol/L, 75 mmol/L and 100 mmol/L significantly inhibited cell growth in a dose-dependent manner compared to the control group (P<0.05), while 25 mmol/L had no effect (P>0.05). The expression level of miR-21-5p also differed significantly in response to different concentrations of metformin (P<0.05). The expression of miR-21-5p mRNA in the 50mmol/L, 75mmol/L and 100mmol/L metformin groups was significantly lower than in the control group (P<0.05). There was no significant difference in the expression of miRNA-21-5p between 25 mmol/L metformin group and control group (P>0.05). There was no significant difference in the expression level of miRNA-21-5p between 50 mmol/L, 75 mmol/L and 100 mmol/L dimethylbismus groups (P>0.05). There was a significant difference in the expression level of PDCD4 in response to different concentrations of metformin (P<0.05). The expression levels of PDCD4 mRNA in FaDu cells rose in dose-dependent manner at concentrations of 50 mmol/L, 75 mmol/L and 100 mmol/L of metformin compared to the control group (P<0.05). However, there was no significant difference between 25 mmol/L metformin group and control group (P>0.05). The expression of PDCD4 in HepG2 cells increased significantly in response to microRNA-21-5p inhibition, compared to controls (P<0.05). 

Conclusion: Metformin significantly inhibited the proliferation of a hypopharyngeal carcinoma cell line. Our results suggest metformin down-regulated the expression of miRNA-21-5p, which then modulated the downstream target PDCD4. The resulting increased expression of the tumor suppressor PDCD4 may be a mechanism by which the drug inhibits cancer cell proliferation.

Keywords

Dimethylbismus, microRNA-21-5p, PDCD4, hypopharyngeal cancer.

DOI:

10.19193/0393-6384_2020_3_228