Effects of metformin and adiponectin on endometrial cancer cells growth / 北京大学学报(医学版)

OBJECTIVE@#To determine the effect of metformin and adiponectin on the proliferation of EC cells and the relationship between metformin and adiponectin.@*METHODS@#The proliferation impact of different concentrations of metformin and adiponectin on two types of EC cells ishikawa (IK) and HEC-1B was confirmed by CCK-8 method. qRT-PCR and Western blot were used to detect the effect of different concentrations of metformin on the changes of adiponectin receptors (AdipoR1 and AdipoR2) of the EC cells both in mRNA and protein level and the role of compound C, an adenosine monophosphate-activated protein kinase (AMPK) inhibitor, on the above effects.@*RESULTS@#(1) Both metformin and adiponectin could significantly promote the proliferation of endometrial cancer (EC) cells in a time and concentration dependent manner (P<0.05).(2)Metformin and adiponectin had synergy anti-proliferative effect on EC cells and the combination index (CI) value of IK cells was 0.906 34 and of HEC-1B cells was 0.827 65. (3)qRT-PCR was used to detect the mRNA levels of AdipoR1 and AdipoR2 after 5 mmol/L and 10 mmol/L metformin, respectively, stimulating IK and HEC-1B cells for 48 hours and the mRNA expressions of AdipoR1 and AdipoR2 were significantly increased when compared with the control group (0 mmol/L)(IK: AdipoR1 of 5 mmol/L and 10 mmol/L group: P<0.001,AdipoR2 of 5 mmol/L group: P<0.001; HEC-1B: AdipoR1 of 5 mmol/L group: P<0.001, 10 mmol/L group: P=0.023, AdipoR2 of 5 mmol/L group: P<0.001, 10 mmol/L group: P=0.024). When combined with compound C, the RNA levels of AdipoR1 and AdipoR2 were not different compared with the control group (0 mmol/L, P>0.05). (4) Western blot was used to detect the protein levels of AdipoR1 and AdipoR2 after 5 mmol/L and 10 mmol/L metformin, stimulating IK and HEC-1B cells for 48 hours and the protein level was significantly increased when compared with the control group (0 mmol/L)(IK: AdipoR1 of 5 mmol/L group: P=0.04, 10 mmol/L group: P=0.033, AdipoR2 of 5 mmol/L group: P=0.044, 10 mmol/L group: P=0.046; HEC-1B: AdipoR1 of 5 mmol/L group: P=0.04, 10 mmol/L group: P=0.049, AdipoR2 of 5 mmol/L group: P=0.043, 10 mmol/L group: P=0.035). When combined with compound C,the protein levels of AdipoR1 and AdipoR2 were not different compared with the control group (0 mmol/L, P>0.05).@*CONCLUSION@#We find that metformin and adiponectin have synergy anti-proliferative effect on EC cells. Besides, metformin can increase adiponectin receptors expressions of EC cells both in mRNA and protein levels and this effect is accomplished by the activation of AMPK signaling pathway.

Effect of High-fat Diet-induced Disorders on Rat with Endometrial Hyperplasia and Adiponectin System in Circulation and Uterus / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Epidemiologic and genetic studies suggest a link between insulin resistance (IR) and endometrial cancer, and endometrial hyperplasia (EH) is a precancerous stage of endometrial cancer. Adiponectin is an adipokine which previously shown to be a risk factor for endometrial cancer. The aim of the study was to develop a rat model of IR and EH and evaluate adiponectin system in circulation and uterus.</p><p><b>METHODS</b>This study was a 46-week animal trial from February 2014 to January 2015. Female Sprague-Dawley rats were fed with high-fat diet (HFD) for 40 weeks to induce IR. Followed by ovariectomization, rats were orally administrated to 17β-estradiol (E2) for 4 weeks to induce EH and then sacrificed. A total of 36 rats were divided into four groups: E2, HFD, HFD + E2, and control groups. Data were analyzed with Student's t-test, one-way analysis of variance (ANOVA), and Mann-Whitney U-tests. Chi-square was used to evaluate the score of immunohistochemistry.</p><p><b>RESULTS</b>The thickness of endometrial, glandular epithelium, and myometrium in the HFD-E2group were higher than the E2group (F = 59.02, F = 23.51 and F = 12.53, respectively, all P < 0.001). Plasma adiponectin levels in the E2group were lower than those in the control group, and the levels in the HFD-E2group were lower than those in the HFD group (F = 13.15, P < 0.05). However, after normalized to visceral adipose tissue, compared to the control group, plasma adiponectin levels were decreased in rat with HFD in the absence or presence of E2, respectively (F = 6.72, P < 0.05). Adiponectin gene (F = 10.48, P < 0.05) and protein (P < 0.05) levels in uterus in the HFD-E2group were higher than those in the HFD group.</p><p><b>CONCLUSIONS</b>This study manifests that IR can effectively modulate EH, which suggests the involvement of energetic metabolism in uterine alternation. The combination effects of IR and EH modulate circulating adiponectin levels. However, adiponectin gene and protein levels in uterus are mainly response to estradiol.</p>