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

甲醛通过PTEN/PI3K/Akt信号转导通路诱导BALB/c小鼠骨髓细胞凋亡

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作者:Guangyan Yu, Chunhua Wang, Xiangfu Song, Shimeng Liu, Yixin Zhang, Lida Fan, Yixue Yang, Yulu Huang, Jiayi Song

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.

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