Nuclear forkhead box O3a accumulation contributing to the proliferative suppression in liver cancer cells byPI3K/Akt signaling pathway
Hou Yibin1, Ge Sun2, Xu Jiang3, Zhongsheng Zhu1, Jijin Yang3
1 Department of Interventional Radiology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Pudong, Shanghai 201399, China
2 Department of Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong, China
3 Department of Interventional Radiology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
Department of Interventional Radiology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433
Source of Support: None, Conflict of Interest: None
Background: Serine/threonine kinase is originally identified as an oncogene and the forkhead box transcription factor forkhead box O3a (Foxo3a) has been found to be decreased in various human cancers. In the present study, we explored the expression of Akt and FOXO3a in liver cancer cells.
Materials and Methods: Akt level was detected by Western blotting analysis. Cell viability of HepG2, MHCC-97H, Bel7402, and L02 was determined by MTT assay. FoxO3a level was determined by Western blotting analysis.
Results: Akt level was significantly higher in liver cancer cell lines HepG2 and MHCC97-H, compared with the immortalized liver cell line L02. MTT assay results demonstrated that LY294002 significantly suppressed cell proliferation of HepG2 and MHCC-97H cells in a dose- and time-dependent manner. The underlying molecular mechanism was that miR-370 inhibited cell proliferation of liver cancer cells by activating FoxO3a.
Conclusion: PI3K inhibitor decreased the levels of phosphorylated FOXO3a and increased the levels of nuclear FOXO3a. It also inhibited cell proliferation of liver cancer cells partly by PI3K/Akt/FOXO3a signaling pathways.