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Insulin Growth Factor-1 (IGF-1) Inhibits Apoptosis of Bone Marrow Mesenchymal Stem Cells (BMSCs) through PI3K/Akt Pathway
Li Xin, Zhu Jing*, Tian Jie, Tan Bin, Cui Xiangrong, Xiang Zhongping
The Children’s Hospital Chongqing Medical University, Ministry of Education Key Laboratory of Developmental Disease in Childhood and Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing 400014, China
Abstract: This study investigated the effect of insulin-like growth factor-1 (IGF-1) on apoptosis of bone marrow mesenchymal stem cells (BMSCs) by constructing an abnormal microenvironment model with high expression of IGF-1 and the possible mechanism， which provided a preliminary experimental basis for the safe application of BMSCs as a carrier for the targeted treatment of tumors. BMSCs were isolated and purified. The surface markers of BMSCs were identified by flow cytometry. The cells were divided into four groups: BMSCs blank control group， IGF-1 stimulation group， IGF-1+LY294002 blocker group and IGF-1+MK2206 blocker group. The morphological changes of the cells were observed under an inverted phase contrast microscope after 2 weeks of drug treatment. The cell proliferation was detected by CCK-8 assay. The morphology and apoptotic ratio of nuclei were observed by Hoechst 33342 staining. The apoptosis and the mitochondria were detected by flow cytometry. The levels of Akt， Bad， Bcl-xl， c-Myc and STAT3 were detected by RT-qPCR. The expressions of Akt， p-Akt， Bad， p-Bad， Bcl-xl， p-STAT3 protein levels were investigated by Western blot. The results showed that compared with blank control group， the proliferation rate of IGF-1 stimulated cells increased and the apoptosis rate decreased; the mRNA levels of Bad， Bcl-xl， c-Myc， STAT3 and the protein expressions of p-Akt， Bad， p-Bad， Bcl-xl， c-Myc， STAT3 and p-STAT3 in BMSCs were significantly higher than that in BMSCs (P<0.05) control group (P<0.05). Compared with IGF-1 stimulated group， the proliferation rate and the apoptosis rate of the cells in the blocking group (IGF-1+LY294002 blocker group and IGF-1+MK2206 blocker group) were lower than those in the IGF-1 stimulated group， and the mRNA and protein expression levels of related molecules were significantly decreased. The results showed that IGF-1 can activate the PI3K/Akt pathway and activate the downstream proliferation and apoptosis-related molecules， thereby promoting the proliferation of BMSCs and inhibiting the apoptosis of BMSCs.
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