Agrawal Siddarth, Łuc Mateusz, Ziółkowski Piotr, Agrawal Anil Kumar, Pielka Ewa, Walaszek Kinga, Zduniak Krzysztof, Woźniak Marta
1 Department of Pathology, Wroclaw Medical University, Wroclaw, Poland.
2 Department of General and Oncological Surgery, Wroclaw Medical University, Wroclaw, Poland.
Tumour Biol. 2017 Jun;39(6):1010428317702901. doi: 10.1177/1010428317702901.
The study was designed to evaluate the potential use of insulin for cancer-specific treatment. Insulin-induced sensitivity of MCF-7 breast cancer cells to chemotherapeutic agents 5-fluorouracil and cyclophosphamide was evaluated. To investigate and establish the possible mechanisms of this phenomenon, we assessed cell proliferation, induction of apoptosis, activation of apoptotic and autophagic pathways, expression of glucose transporters 1 and 3, formation of reactive oxygen species, and wound-healing assay. Additionally, we reviewed the literature regarding theuse of insulin in cancer-specific treatment. We found that insulin increases the cytotoxic effect of 5-fluorouracil and cyclophosphamide in vitro up to two-fold. The effect was linked to enhancement of apoptosis, activation of apoptotic and autophagic pathways, and overexpression of glucose transporters 1 and 3 as well as inhibition of cell proliferation and motility. We propose a model for insulin-induced sensitization process. Insulin acts as a sensitizer of cancer cells to cytotoxic therapy through various mechanisms opening a possibility for metronomic insulin-based treatments.
本研究旨在评估胰岛素在癌症特异性治疗中的潜在用途。评估了胰岛素诱导MCF-7乳腺癌细胞对化疗药物5-氟尿嘧啶和环磷酰胺的敏感性。为了研究并确定这种现象的可能机制，我们评估了细胞增殖、凋亡诱导、凋亡和自噬途径的激活、葡萄糖转运蛋白1和3的表达、活性氧的形成以及伤口愈合试验。此外，我们查阅了有关胰岛素在癌症特异性治疗中应用的文献。我们发现胰岛素在体外可将5-氟尿嘧啶和环磷酰胺的细胞毒性作用提高两倍。这种作用与凋亡增强、凋亡和自噬途径的激活、葡萄糖转运蛋白1和3的过表达以及细胞增殖和运动的抑制有关。我们提出了一个胰岛素诱导致敏过程的模型。胰岛素通过各种机制作为癌细胞对细胞毒性治疗的致敏剂，为基于胰岛素的节拍式治疗开辟了可能性。
