Cancer Pre Res：药物二甲双胍或有助预防原发性肝癌

近日，美国马里兰大学医学院研究人员日前公布研究报告称，他们完成的动物研究显示，常用糖尿病药物二甲双胍或许有助于预防原发性肝癌。美国《癌症预防研究》Cancer Prevention Research杂志4月刊以封面文章的形式刊登了相关研究报告。

研究人员培育了一批易患原发性肝癌的模型小鼠，然后给其中部分小鼠食物中添加二甲双胍。他们发现，服用二甲双胍的小鼠患原发性肝癌的比例比对照组低57%；服药后仍患癌的小鼠肿瘤大小比对照组平均小37%。

领导研究的杰弗里·戈农表示，基于这项发现，医学界应该评估是否将二甲双胍列为原发性肝癌的预防药物。

二甲双胍是一种具有长期用药安全记录的药品。此前曾有研究显示，二甲双胍可抑制肺部和乳腺肿瘤的生长，降低糖尿病患者患胰腺癌和乳腺癌的风险。（生物谷：Bioon.com）

doi:10.1158/1940-6207.CAPR-11-0228
PMC:
PMID:

Metformin Prevents Liver Tumorigenesis by Inhibiting Pathways Driving Hepatic Lipogenesis

Kavita Bhalla1, Bor Jang Hwang1, Ruby E. Dewi1, William Twaddel2, Olga G. Goloubeva1, Kwok-Kin Wong4, Neeraj K. Saxena1, Shyam Biswal3, and Geoffrey D. Girnun1

A number of factors have been identified that increase the risk of hepatocellular carcinoma (HCC). Recently it has become appreciated that type II diabetes increases the risk of developing HCC. This represents a patient population that can be identified and targeted for cancer prevention. The biguanide metformin is a first-line therapy for the treatment of type II diabetes in which it exerts its effects primarily on the liver. A role of metformin in HCC is suggested by studies linking metformin intake for control of diabetes with a reduced risk of HCC. Although a number of preclinical studies show the anticancer properties of metformin in a number of tissues, no studies have directly examined the effect of metformin on preventing carcinogenesis in the liver, one of its main sites of action. We show in these studies that metformin protected mice against chemically induced liver tumors. Interestingly, metformin did not increase AMPK activation, often shown to be a metformin target. Rather metformin decreased the expression of several lipogenic enzymes and lipogenesis. In addition, restoring lipogenic gene expression by ectopic expression of the lipogenic transcription factor SREBP1c rescues metformin-mediated growth inhibition. This mechanism of action suggests that metformin may also be useful for patients with other disorders associated with HCC in which increased lipid synthesis is observed. As a whole these studies show that metformin prevents HCC and that metformin should be evaluated as a preventive agent for HCC in readily identifiable at-risk patients. Cancer Prev Res; 5(4); 544–52. ©2012 AACR.