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Archive > Volume 21 Issue 2 > 2014,21(2):153-159. DOI:10.3872/j.issn.1007-385X.2014.02.007 Prev Next
Basic Research
Synergistic effects and underlying mechanisms of liver kinase B1 and metformin on proliferation and apoptosis of cervical cancer cells and its spossible mechanism
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Abstract:
Objective : To explore synergistic effects and the underlying mechanisms of liver kinase B1 ( LKB1 ) or serine-threonine kinase 11 ( STK11 ) and metformin on proliferation and apoptosis of human cervical cancer cells using the HeLa cell line as a model. Methods: A recombinant plasmid LKB1-pEGFP-n1 was constructed. HeLa cells were transfected with this construct and the mock-vehicle pEGFP-n1 respectively. Transfectants were then treated with metformin. Cell viability was assessed by MTT assays, apoptosis and cycle progression by flow cytometry, and phosphorylation of AMRK, ACC and Rb (key players in the LKB1-AMPK signaling pathway) by Western blotting, 24 h after metformin treatment. Results: Both LKB1-pEGFP-n1 and the mock-vehicle pEGFP-n1 were successfully transfected into HeLa cells. After metformin treatment, IC50 was significantly lower in cells transfected with LKB1-pEGFP-n1(2.9±0.4) mmol/L than those transfected with pEGFP-n1 (7.8±1.3) mmol/L and wild type HeLa cells (9.6±1.5) mmol/L (P<0.01), indicating a significant cell growth-inhibiting effect for LKB1. LKB1-pEGFP-n1 group showed a G1 phase arrest after treatment with metformin. In contrast, no cell cycle arrest was evident in wild type Hela cells or HeLa cells transfected with pEGFP-n1. After treatment with 15 mmol/L metformin, apoptosis rate was significantly higher in cells transfected with LKB1-pEGFP-n1 (28.6±2.3)% than that in cells transfected with pEGFP-n1 (9.6±1.6)% and wild type cells (17.8±1.9)% (P<0.05). Phosphorylation of AMPKα and ACC was increased but phosphorylation of Rb was decreased in cells transfected with LKB1-pEGFP-n1 as compared with untransfected cells and cells transfected with pEGFP-n1. Conclusion: LKB1 and metformin may affect the proliferation and apoptosis of cervical cancer cells in a coordinated manner, possibly involving the LKB1-AMPK signaling pathway.
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Project Supported:
Project supported by the Medical Technology Innovation Topics from Nanjing Military Area Command of PLA（No.11MA072)
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