Mfn2 inhibits proliferation and cell-cycle in Hela cells via Ras-NF-κB signal pathway.

BACKGROUND

Mitofusin 2 (Mfn2) is outer membrane protein, as the inhibitor of Ras protein. This study aimed to investigate the effect of Mfn2 on cell proliferation, and cell-cycle in Hela cervical carcinoma cell lines.

METHODS

After treated with Adv-mfn2 or Adv-control for 48 h and 60 h, the RNA and protein of Mfn2 in Hela cells were detected by qRT-PCR and western blot. The immunofluorescence assay was performed to observe the expression and sub-location of Mfn2 in Hela cells. The flow cytometry was performed to detect the cell cycle of Hela cells, while western blots were performed to observe the Ras-NF-κB signal pathway. Then, the xenografted cervix carcinoma mouse model was used to confirm the effect of Mfn2 in Hela cells in vivo and the expression of Ras-NF-κB signaling pathway in vivo.

RESULTS

In immunofluorescence detection, Mfn2 was located in cytoplasmic, not in the nucleus. In addition, Mfn2 inhibited cell proliferation of Hela cells through reducing PCNA protein expression. Mfn2 induced arrest in G0/G1 phase of the cell cycle in Hela cells. Meanwhile, Mfn2 reduced Cyclin D1 protein expression. Moreover, Mfn2 decreased the Ras signal pathway proteins such as Myc, NF-κB p65, STAT3 in a dose-dependent manner. Then, the in vivo experiment also confirmed that Mfn2 could inhibit the tumor growth, and depress the Cyclin D1, Ras, Myc, NF-κB p65, Erk1/2 and mTOR protein expression.

CONCLUSIONS

Mfn2 could significantly inhibit cell proliferation in Hela cells. It might be acted as an potential anti-cancer target through inducing cell cycle arrest in human cervical carcinoma cells.