Metformin attenuates the stimulatory effect of a high-energy diet on in vivo LLC1 carcinoma growth
Metformin attenuates the stimulatory effect of a high-energy diet on in vivo LLC1 carcinoma growth
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DOI：
10.1677/erc-08-0038
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发表时间：
2008-09-01
影响因子：
3.9
通讯作者：
Pollak, Michael
中科院分区：
文献类型：
--
作者：
Algire, Carolyn;Zakikhani, Mahvash;Pollak, Michael
我们研究了二甲双胍对C57 BL/6 J小鼠刘易斯肺癌LLC 1生长的影响，这些小鼠提供对照饮食或高能量饮食，先前报道导致体重增加和全身胰岛素抵抗伴高胰岛素血症。将48只雄性小鼠随机分为4组：对照饮食、对照饮食+二甲双胍、高能量饮食或高能量饮食+二甲双胍。在实验饮食8周后，选定的组在其饮用水中接受二甲双胍。二甲双胍治疗开始后3周，向小鼠注射0.5 × 10（6）个LLC 1细胞，并测量肿瘤生长17天。到第17天，高能量饮食小鼠的肿瘤体积几乎是对照饮食小鼠的两倍。二甲双胍显著减弱了饮食对肿瘤生长的影响，但二甲双胍对对照饮食小鼠的肿瘤生长没有影响。二甲双胍减弱了与高能量饮食相关的胰岛素受体活化增加，也导致AMP激酶磷酸化增加，这两种作用预计会减少肿瘤增殖。这些实验结果与先前的假设产生流行病学研究一致，这些研究表明二甲双胍可能降低癌症风险并改善癌症预后。最后，这些结果为评价二甲双胍在高胰岛素血症癌症患者中的抗肿瘤活性提供了依据。内分泌相关癌症（2008）15 833-839
We investigated the effects of metformin on the growth of lewis lung LLC1 carcinoma in C57BL/6J mice provided with either a control diet or a high-energy diet, previously reported to lead to weight gain and systemic insulin resistance with hyperinsulinemia. Forty-eight male mice were randomized into four groups: control diet, control diet+metformin, high-energy diet, or high-energy diet+metformin. Following 8 weeks on the experimental diets, selected groups received metformin in their drinking water. Three weeks following the start of metformin treatment, mice were injected with 0.5 x 10(6) LLC1 cells and tumor growth was measured for 17 days. By day 17, tumors of mice on the high-energy diet were nearly twice the volume of those of mice on the control diet. This effect of diet on tumor growth was significantly attenuated by metformin, but metformin had no effect on tumor growth of the mice on the control diet. Metformin attenuated the increased insulin receptor activation associated with the high-energy diet and also led to increased phosphorylation of AMP kinase, two actions that would be expected to decrease neoplastic proliferation. These experimental results are consistent with prior hypothesis-generating epidemiological studies that suggest that metformin may reduce cancer risk and improve cancer prognosis. Finally, these results contribute to the rationale for evaluation of the anti-neoplastic activity of metformin in hyperinsulinemic cancer patients. Endocrine-Related Cancer (2008) 15 833-839