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[Antiproliferative effects of LY294002 on MCL Jeko-1 cell line and its mechanism]
Hong-Pu Chen1, Yi-Qun Huang, Xu-Dong Ma
1Department of Hematology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou 363000, Fujian Province, China.
Abstract:
This study was aimed to investigate the effects of LY294002, a specific inhibitor of phosphatidylinositol 3-kinase, on growth and apoptosis of MCL Jeko-1 cell line and its mechanism. The proliferation inhibitory rate of Jeko-1 cells treated by different doses of LY294002 was assayed by MTT method; the level of apoptosis of Jeko-1 cells was detected by flow cytometry; the expression level of apoptosis-related protein Cyclin D1, Bcl-2, procaspase-3 and PI3K/Akt signaling pathway protein phosphorylated-Akt (p-Akt), phosphorylated-TOR (p-mTOR), phosphorylated-P70S6K (p-P70S6K) phosphorylated-Akt (p-Akt) in Jeko-1 cells were determined by Western blot. The results showed that the growth of Jeko-1 cell line was inhibited by LY294002. The apoptosis rates of Jeko-1 cells treated with 0, 5, 10 and 20 µmol/L of LY294002 for 24 hours were (3.25 ± 1.27)%, (11.34 ± 2.35)%, (22.81 ± 2.74)%, (43.61 ± 3.48)% respectively, the difference between them was statistically significant (P < 0.01). Phosphorylation levels of PI3K/Akt signaling pathway protein p-Akt, p-mTOR, p-P70S6K decreased, the expression of apoptosis-related protein cyclin D1, Bcl-2, procaspase-3 was down-regulated.It is concluded that the LY294002 can inhibit Jeko-1 cell proliferation, which may be realized through down-regulating the phosphorylation level of p-Akt, p-mTOR, p-P70S6K, inhibiting the P13k/Akt signaling pathway, and promoting the cell apoptosis.
Insights
LY294002, a phosphatidylinositol 3-kinase inhibitor, effectively suppresses Jeko-1 cell proliferation and induces apoptosis. This occurs by down-regulating the PI3K/Akt signaling pathway, impacting key proteins involved in cell growth and survival.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Mantle cell lymphoma (MCL) is an aggressive non-Hodgkin lymphoma.
- The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway plays a crucial role in cell proliferation and survival, making it a target for cancer therapy.
- LY294002 is a well-characterized inhibitor of PI3K.
Purpose of the Study:
- To investigate the effects of LY294002 on the proliferation and apoptosis of the MCL Jeko-1 cell line.
- To elucidate the underlying mechanism of LY294002's action on Jeko-1 cells, focusing on the PI3K/Akt signaling pathway.
Main Methods:
- MTT assay was used to determine the proliferation inhibitory rate of Jeko-1 cells treated with varying doses of LY294002.
- Flow cytometry was employed to detect the apoptosis level in Jeko-1 cells.
- Western blot analysis was performed to assess the expression levels of apoptosis-related proteins (Cyclin D1, Bcl-2, procaspase-3) and PI3K/Akt pathway proteins (p-Akt, p-mTOR, p-P70S6K).
Main Results:
- LY294002 significantly inhibited Jeko-1 cell proliferation in a dose-dependent manner.
- Apoptosis rates increased significantly with increasing concentrations of LY294002 (e.g., 43.61% at 20 µmol/L vs. 3.25% in control).
- LY294002 treatment led to decreased phosphorylation of PI3K/Akt pathway proteins (p-Akt, p-mTOR, p-P70S6K) and down-regulation of Cyclin D1, Bcl-2, and procaspase-3 expression.
Conclusions:
- LY294002 effectively inhibits Jeko-1 cell proliferation.
- The anti-proliferative and pro-apoptotic effects of LY294002 are mediated through the inhibition of the PI3K/Akt signaling pathway.
- Targeting the PI3K/Akt pathway with LY294002 presents a potential therapeutic strategy for MCL.
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