Formaldehyde induces the apoptosis of BMCs of BALB/c mice via the PTEN/PI3K/Akt signal transduction pathway.

Abstract

The International Agency for Research on Cancer has classified formaldehyde (FA) as a leukemogen to humans in 2012; however, the underlying mechanism remains unclear. Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a tumor-suppressor gene and can negatively regulate the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signal transduction pathway, which is associated with cell proliferation, apoptosis and carcinogenesis. To determine the association between FA and the PTEN/PI3K/Akt signal transduction pathway, flow cytometry, reverse transcription-quantitative polymerase chain reaction, western blotting and immunohistochemical analysis were conducted. Bone marrow cells were obtained from BALB/c mice, divided into the control (untreated cells) and FA groups, which were treated with various doses of FA (50, 100 and 200 µmol/l). Following treatment with FA for 24 h, cell viability, the cell cycle, apoptosis, and the expression of PTEN, PI3K and Akt, as well as the protein expression of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X (Bax), and Caspases-3 and −9 were examined. Furthermore, 10 µmol/PI3K inhibitor (LY294002) was applied to inhibit the PTEN/PI3K/Akt signal transduction pathway and 100 µmol/l FA was selected for treatment; alteration in the cell cycle were analyzed. The results demonstrated that FA could suppress cell viability, and downregulate PTEN and Bcl-2; the expression of PI3K, Akt, Bax, and Caspases-3 and −9 were upregulated. Additionally, FA was reported to induce cell cycle arrest at the G0/G1 phase and apoptosis. Following the application of LY294002 to inhibit the PTEN/PI3K/Akt signal transduction pathway, the numbers of cells arrested in the G0/G1 phase were significantly increased in the PI3K inhibitor group compared with the control (P<0.01); however, no significant change in the number of G0/G1 cells compared with FA group was observed (P>0.05). The results of the present study suggested that the PTEN/PI3K/Akt signal transduction pathway served an important role in the process of FA-induced apoptosis, which may be associated with regulating the cell cycle; thus, cell proliferation may be affected.