Phenformin as prophylaxis and therapy in breast cancer xenografts.
Phenformin as prophylaxis and therapy in breast cancer xenografts.
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苯甲曲作为预防和乳腺癌异种移植的治疗。
DOI：
10.1038/bjc.2012.56
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发表时间：
2012-03-13
影响因子：
8.8
通讯作者：
Thompson, A. M.
中科院分区：
文献类型：
--
作者：
Appleyard, M. V. C. L.;Murray, K. E.;Coates, P. J.;Wullschleger, S.;Bray, S. E.;Kernohan, N. M.;Fleming, S.;Alessi, D. R.;Thompson, A. M.
观察到用双胍类药物治疗的糖尿病患者患癌症的风险降低，这激发了人们将这些药物用作抗癌疗法的热情。我们试图确定苯乙双胍在免疫功能低下小鼠中对雌激素受体（ER）阳性的MCF7和受体三阴性的MDAMB231异种移植物进行化学预防和治疗的功效。我们还比较了苯乙双胍和二甲双胍在治疗MDAMB231中的功效。
将免疫功能低下的小鼠分为几组：（1）在细胞注射前2周给予苯乙双胍；（2）用苯乙双胍治疗已形成的肿瘤；（3）用二甲双胍治疗已形成的肿瘤（仅针对MDAMB231肿瘤）；（4）未治疗的对照组。采集治疗后的肿瘤、肝脏和脾脏进行进一步分析。
苯乙双胍显著抑制MCF7和MDAMB231肿瘤的发生和生长，并且对于MDAMB231，其效果比二甲双胍更好，且对小鼠无毒性。与对照组相比，苯乙双胍治疗的异种移植物中有丝分裂象的数量显著减少。结果表明，苯乙双胍在体内的作用机制与AMPK激活一致。
苯乙双胍作为一种抗肿瘤药物具有临床潜力，应考虑在ER阳性和三阴性乳腺癌中进行临床试验。
Observations that diabetics treated with biguanide drugs have a reduced risk of developing cancer have prompted an enthusiasm for these agents as anti-cancer therapies. We sought to determine the efficacy of the biguanide phenformin in the chemoprophylaxis and in the treatment of oestrogen receptor (ER)-positive MCF7 and receptor triple-negative MDAMB231 xenografts in immunocompromised mice. We also compared the efficacy of phenformin and metformin in the treatment of MDAMB231. Immunocompromised mice were divided into groups: (1) phenformin administered for 2 weeks prior to cell injection; (2) established tumours treated with phenformin; (3) established tumours treated with metformin (only for MDAMB231 tumours); (4) untreated controls. Post-treatment tumours, liver and spleen were harvested for further analysis. Phenformin significantly inhibited both the development and growth of MCF7 and MDAMB231 tumours, and for MDAMB231 at greater efficacy than metformin without murine toxicity. The number of mitotic figures was significantly fewer in xenografts treated with phenformin compared with controls. Results suggested that the mechanism of action of phenformin in vivo is consistent with AMPK activation. Phenformin has clinical potential as an antineoplastic agent and should be considered for clinical trials both in ER-positive and triple-negative breast cancer.
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影响因子：
8
作者：
Chlenski, A.;Guerrero, L. J.;Cohn, S. L.
通讯作者：
Cohn, S. L.
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：
3.9
作者：
Anisimov, VN;Berstein, LM;Franceschi, C
通讯作者：
Franceschi, C
影响因子：
9.7
作者：
DILMAN, VM;ANISIMOV, VN
通讯作者：
ANISIMOV, VN
影响因子：
6.4
作者：
Chlenski, A;Liu, SQ;Cohn, SL
通讯作者：
Cohn, SL