The impact of type 2 diabetes and antidiabetic drugs on cancer cell growth.
The impact of type 2 diabetes and antidiabetic drugs on cancer cell growth.
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DOI：
10.1111/j.1582-4934.2010.01083.x
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发表时间：
2011-04
影响因子：
5.3
通讯作者：
Yeung SC
中科院分区：
文献类型：
--
作者：
Feng YH;Velazquez-Torres G;Gully C;Chen J;Lee MH;Yeung SC
尽管对2型糖尿病和癌症的联系机制进行了调查，但对癌症患者糖尿病的药物治疗方面的知识存在差距。流行病学研究表明，糖尿病癌症患者接受不同的降糖治疗有不同的存活率。临床上相关的问题是，一些抗糖尿病药物是否促进癌症，而其他药物是否抑制癌症进展。我们使用四种人类细胞系(胰腺癌：MiaPaCa2，PANC-1；乳腺癌：MCF7，HER18)，研究了不同的抗糖尿病药物对癌细胞有不同直接影响的假设。我们发现胰岛素和葡萄糖促进了癌细胞的增殖，并导致了化疗耐药。二甲双胍和罗格列酮抑制癌细胞生长并诱导细胞凋亡。这两种药物都影响了蛋白激酶B(AKT)/哺乳动物雷帕霉素途径靶点的信号；二甲双胍激活了一磷酸腺苷(AMP)激活的蛋白激酶，而罗格列酮则增加了染色体10的水平。虽然较高的胰岛素和葡萄糖浓度促进了化疗耐药，但二甲双胍或罗格列酮与吉西他滨或阿霉素联合使用时，活体癌细胞进一步减少，细胞凋亡率增加。相比之下，埃克塞那肽对癌细胞没有直接作用。综上所述，不同类型的抗糖尿病药物治疗对癌细胞有不同的直接影响。这项研究为进一步研究二甲双胍和罗格列酮作为癌症患者2型糖尿病的一线治疗方法提供了实验证据。
Despite investigations into mechanisms linking type 2 diabetes and cancer, there is a gap in knowledge about pharmacotherapy for diabetes in cancer patients. Epidemiological studies have shown that diabetic cancer patients on different antidiabetic treatments have different survival. The clinically relevant question is whether some antidiabetic pharmacotherapeutic agents promote cancer whereas others inhibit cancer progression. We investigated the hypothesis that various antidiabetic drugs had differential direct impact on cancer cells using four human cell lines (pancreatic cancer: MiaPaCa2, Panc-1; breast cancer: MCF7, HER18). We found that insulin and glucose promoted cancer cell proliferation and contributed to chemoresistance. Metformin and rosiglitazone suppressed cancer cell growth and induced apoptosis. Both drugs affected signalling in the protein kinases B (AKT)/mammalian target of rapamycin pathway; metformin activated adenosine monophosphate (AMP)-activated protein kinase whereas rosiglitazone increased chromosome ten level. Although high insulin and glucose concentrations promoted chemoresistance, the combination of metformin or rosiglitazone with gemcitabine or doxorubicin, resulted in an additional decrease in live cancer cells and increase in apoptosis. In contrast, exenatide did not have direct effect on cancer cells. In conclusion, different types of antidiabetic pharmacotherapy had a differential direct impact on cancer cells. This study provides experimental evidence to support further investigation of metformin and rosiglitazone as first-line therapies for type 2 diabetes in cancer patients.
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罗格列酮通过干扰IGF-IR细胞内信号传导来抑制肾上腺皮质癌细胞的增殖。
影响因子：
2.9
作者：
Cantini, Giulia;Lombardi, Adriana;Piscitelli, Elisabetta;Poli, Giada;Ceni, Elisabetta;Marchiani, Sara;Ercolino, Tonino;Galli, Andrea;Serio, Mario;Mannelli, Massimo;Luconi, Michaela
通讯作者：
Luconi, Michaela
影响因子：
8.8
作者：
Nilsen TI;Vatten LJ
通讯作者：
Vatten LJ
影响因子：
45.3
作者：
Jiralerspong, Sao;Palla, Shana L.;Gonzalez-Angulo, Ana M.
通讯作者：
Gonzalez-Angulo, Ana M.
影响因子：
5
作者：
Coughlin, SS;Calle, EE;Thun, MJ
通讯作者：
Thun, MJ
影响因子：
4.3
作者：
Dong, Yu-Wei;Wang, Xing-Peng;Wu, Kai
通讯作者：
Wu, Kai