Metformin Increases Sensitivity of Pancreatic Cancer Cells to Gemcitabine by Reducing CD133+ Cell Populations and Suppressing ERK/P70S6K Signaling.
Metformin Increases Sensitivity of Pancreatic Cancer Cells to Gemcitabine by Reducing CD133+ Cell Populations and Suppressing ERK/P70S6K Signaling.
复制标题
二甲双胍通过减少 CD133( ) 细胞群并抑制 ERK/P70S6K 信号传导来增加胰腺癌细胞对吉西他滨的敏感性。
DOI：
10.1038/srep14404
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发表时间：
2015-09-22
影响因子：
4.6
通讯作者：
Gou S
中科院分区：
文献类型：
--
作者：
Chai X;Chu H;Yang X;Meng Y;Shi P;Gou S
胰腺癌的预后仍然很差，由于其高频率的化疗耐药，化疗进展甚微。二甲双胍被广泛用于治疗II型糖尿病，最近被证明可以抑制胰腺癌干细胞增殖。在本研究中，我们研究了二甲双胍在胰腺癌细胞对吉西他滨化疗耐药中的作用，及其可能的细胞和分子机制。二甲双胍增加胰腺癌细胞对吉西他滨的敏感性。其机制至少部分涉及通过抑制ERK磷酸化来抑制CD133+细胞增殖和抑制P70S6K信号传导激活。原发性肿瘤样本的研究揭示了P70S6K信号转导激活与胰腺癌恶性程度之间的关系。临床数据分析显示二甲双胍对胰腺癌合并糖尿病患者的获益趋势。结果提示，二甲双胍在克服胰腺癌化疗耐药方面具有潜在的临床应用价值。
The prognosis of pancreatic cancer remains dismal, with little advance in chemotherapy because of its high frequency of chemoresistance. Metformin is widely used to treat type II diabetes, and was shown recently to inhibit pancreatic cancer stem cell proliferation. In the present study, we investigated the role of metformin in chemoresistance of pancreatic cancer cells to gemcitabine, and its possible cellular and molecular mechanisms. Metformin increases sensitivity of pancreatic cancer cells to gemcitabine. The mechanism involves, at least in part, the inhibition of CD133+ cells proliferation and suppression of P70S6K signaling activation via inhibition of ERK phosphorylation. Studies of primary tumor samples revealed a relationship between P70S6K signaling activation and the malignancy of pancreatic cancer. Analysis of clinical data revealed a trend of the benefit of metformin for pancreatic cancer patients with diabetes. The results suggested that metformin has a potential clinical use in overcoming chemoresistance of pancreatic cancer.