Abstract: Background and purpose: Adiponectin (APN) is considered to be a potent anti-cancer factor that inhibits tumor cell growth, but the mechanism by which APN regulates cell metastasis remains unclear. This study investigated whether APN can pass AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/phosphorylated eukaryotic promoter 4E binding protein 1 (4EBP1) in endometrial cancer HEC-1B cells to inhibit cell migration and invasion. Methods: There were 4 experimental groups: ① APN group: 20 μg/mL APN treated cells for 30 min; ② inhibitor group: 10 μmol/L complex C (AMPK inhibitor) treated cells for 30 min; ③ APN+inhibitor group: 10 μmol/L complex C pretreated cells for 30 min followed by incubation with 20 μg/mL APN for 30 min; ④ control group: only serum-free DMEM medium was added. The expression levels of B cell lymphoma-2 (Bcl-2) and matrix metallopeptidase 9 (MMP-9) mRNA in 4 groups of cells were detected by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR). Western blot was used to detect the protein activation levels of AMPK, mTOR and 4EBP1 in Bcl-2, MMP-9 and AMPK signaling pathways in 4 groups of cells. Transwell and scratch assays were used to detect the migration ability of HEC-1B cells in four groups. Results: The expression levels of Bcl-2 and MMP-9 mRNA in the APN group were 0.64±0.08 and 0.68±0.02, respectively, which were significantly lower than those in the APN+inhibitor group (0.98±0.11 and 0.96±0.08; P=0.02 and 0.03). In the APN group, the protein expressions of Bcl-2 and MMP-9 in HEC-1B cells were significantly different from those in the control group, inhibitor group and APN+ inhibitor group (P=0.00). The activation levels of AMPK, mTOR and 4EBP1 proteins in HEC-1B cells of APN group were 1.49±0.02, 0.48±0.00 and 0.19±0.00, respectively. Protein levels were significantly enhanced compared with the control group (P=0.00). The number of transmembrane cells was 78.72±10.74 in the APN group, 131.45±9.11 in the APN+ inhibitor group, and 131.91±12.29 in the control group. The difference in the number of transmembrane cells between the APN group and the control group was statistically significant (P=0.00), while there was no significant difference between the APN+ inhibitor group and the control group (P=0.12). The mobility of HEC-1B cells in AP-N group was (19.27±1.60)%, which was significantly lower than that of the control group ［(66.51±1.19)%］. The difference in the mobility of HEC-1B cells between the four groups was statistically significant (P=0.00), while there was no significant difference between the three groups (F=2.78, P=0.39). Conclusion: APN can inhibit the migration and invasion of endometrial cancer cells through AMPK/mTOR/4EBP1 signaling pathway and achieve its anti-tumor effect.

Key words: Endometrial neoplasms, Adiponectin, AMP-activated protein kinases, 4E binding protein 1