Zhang Jia-Wei, Zhao Fan, Sun Qing
Department of Oncology, Wuxi No. 2 People's Hospital, Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214000, P.R. China.
Oncol Lett. 2018 Feb;15(2):1811-1816. doi: 10.3892/ol.2017.7444. Epub 2017 Nov 20.
Previous studies have suggested that metformin may improve the survival rate of patients with pancreatic cancer (PC) by regulating the adenosine monophosphate-activated protein kinase/mammalian target of rapamycin (mTOR) signaling pathway. Rapamycin specifically targets mTOR. In the present study, the efficacy of metformin and rapamycin in isolation and combination were investigated for the treatment of PC. The efficacy of metformin and rapamycin in reducing the proliferation of PC cell line SW1990 and was evaluated. It was revealed that metformin (10 mmol/l) + rapamycin (2 ng/ml), metformin (15 mmol/l) + rapamycin (20 ng/ml) and metformin (20 mmol/l) + rapamycin (200 ng/ml) significantly inhibited the viability of PC cells compared with untreated cells. Additionally, metformin (20 mmol/l) + rapamycin (200 ng/ml) significantly suppressed the expression of phosphorylated mTOR compared with metformin or rapamycin alone. Using a xenograft tumor model, it was revealed that combination treatment significantly inhibited the growth of PC cells compared with monotherapy. The present study revealed that a combination of metformin and rapamycin synergistically inhibited the growth of PC and and may be a potential treatment option for patients with PC.
先前的研究表明,二甲双胍可能通过调节腺苷单磷酸活化蛋白激酶/雷帕霉素哺乳动物靶点(mTOR)信号通路来提高胰腺癌(PC)患者的生存率。雷帕霉素特异性作用于mTOR。在本研究中,对二甲双胍和雷帕霉素单独及联合使用治疗PC的疗效进行了研究。评估了二甲双胍和雷帕霉素对PC细胞系SW1990增殖的抑制效果。结果显示,与未处理的细胞相比,二甲双胍(10 mmol/l)+雷帕霉素(2 ng/ml)、二甲双胍(15 mmol/l)+雷帕霉素(20 ng/ml)和二甲双胍(20 mmol/l)+雷帕霉素(200 ng/ml)显著抑制了PC细胞的活力。此外,与单独使用二甲双胍或雷帕霉素相比,二甲双胍(20 mmol/l)+雷帕霉素(200 ng/ml)显著抑制了磷酸化mTOR的表达。使用异种移植肿瘤模型,结果显示与单一疗法相比,联合治疗显著抑制了PC细胞的生长。本研究表明,二甲双胍和雷帕霉素联合使用可协同抑制PC的生长,可能是PC患者的一种潜在治疗选择。