Low concentrations of metformin selectively inhibit CD133⁺ cell proliferation in pancreatic cancer and have anticancer action.
Low concentrations of metformin selectively inhibit CD133⁺ cell proliferation in pancreatic cancer and have anticancer action.
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DOI：
10.1371/journal.pone.0063969
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wang C
中科院分区：
文献类型：
--
作者：
Gou S;Cui P;Li X;Shi P;Liu T;Wang C
胰腺癌是美国癌症相关死亡的第四大原因。预后仍然很差，治疗进展甚微。二甲双胍是一种广泛用于治疗II型糖尿病的药物。最近的流行病学数据显示，口服二甲双胍与降低胰腺癌的风险有关，这表明它有可能成为治疗这种疾病的新药。许多研究已经证明了二甲双胍的体外抗癌作用，但典型的使用浓度远远高于推荐的治疗剂量的体内血浆和组织浓度，而且低浓度的二甲双胍对胰腺癌细胞的增殖几乎没有影响。我们检测了低浓度二甲双胍对不同亚群胰腺癌细胞的影响，发现这些细胞选择性地抑制CD133+细胞的增殖，但不抑制CD24+CD44+ESA+细胞的增殖。我们还检测了低浓度二甲双胍对细胞侵袭和体内肿瘤形成的影响，展示了体外和体内的抗癌作用。二甲双胍可降低磷酸化ERK和磷酸化mTOR，而不依赖Akt和AMPK的磷酸化。CD133+胰腺癌细胞被认为是胰腺癌复发、转移和抵抗辅助治疗的肿瘤干细胞。我们的研究结果为二甲双胍联合现有治疗方法改善该病的预后提供了依据。
Pancreatic cancer is the fourth leading cause of cancer related deaths in the United States. The prognosis remains dismal with little advance in treatment. Metformin is a drug widely used for the treatment of type II diabetes. Recent epidemiologic data revealed that oral administration of metformin is associated with a reduced risk of pancreatic cancer, suggesting its potential as a novel drug for this disease. Many studies have demonstrated the in vitro anticancer action of metformin, but the typically used concentrations were much higher than the in vivo plasma and tissue concentrations achieved with recommended therapeutic doses of metformin, and low concentrations of metformin had little effect on the proliferation of pancreatic cancer cells. We examined the effect of low concentrations of metformin on different subpopulations of pancreatic cancer cells and found that these selectively inhibited the proliferation of CD133+ but not CD24+CD44+ESA+ cells. We also examined the effect of low concentrations of metformin on cell invasion and in vivo tumor formation, demonstrating in vitro and in vivo anticancer action. Metformin was associated with a reduction of phospho-Erk and phospho-mTOR independent of Akt and AMPK phosphorylation. CD133+ pancreatic cancer cells are considered to be cancer stem cells that contribute to recurrence, metastasis and resistance to adjuvant therapies in pancreatic cancer. Our results provide a basis for combination of metformin with current therapies to improve the prognosis of this disease.
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影响因子：
11.2
作者：
Kisfalvi K;Eibl G;Sinnett-Smith J;Rozengurt E
通讯作者：
Rozengurt E
影响因子：
--
作者：
Del Barco S;Vazquez-Martin A;Cufí S;Oliveras-Ferraros C;Bosch-Barrera J;Joven J;Martin-Castillo B;Menendez JA
通讯作者：
Menendez JA
影响因子：
4.8
作者：
Carriere, Audrey;Romeo, Yves;Roux, Philippe P.
通讯作者：
Roux, Philippe P.
DOI：
10.1158/1940-6207.capr-11-0299
发表时间：
2012-03
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Bao B;Wang Z;Ali S;Ahmad A;Azmi AS;Sarkar SH;Banerjee S;Kong D;Li Y;Thakur S;Sarkar FH
通讯作者：
Sarkar FH
影响因子：
11.5
作者：
Rocha, Guilherme Z.;Dias, Marilia M.;Carvalheira, Jose B. C.
通讯作者：
Carvalheira, Jose B. C.