Institute of Medical Biology, Polish Academy of Sciences, Lodz, Poland.
Redox Biol. 2015 Aug;5:420. doi: 10.1016/j.redox.2015.09.031. Epub 2015 Dec 30.
Despite significant improvements in the conventional anti-ovarian cancer therapies, tumor cell resistance to various cytostatic drugs remains a relevant problem. Therefore, the new cancer treatment strategies are being developed. Among many agents that have been studied for their potential anti-cancer activity, the most promising are the nitric oxide (NO) donors-syntethic compounds that release NO in vivo and/or in vitro.
We have evaluated the effect of NO donors on the SK-OV-3 and OVCAR-3 ovarian cancer cell lines. We assessed some of the cancer cells' specific features: the uncontrolled proliferation, over-activation of particular signaling proteins, high resistance to therapeutics and elevated expression and secretion of invasiveness/metastatic factors.
Two members of NONOates family were used: SPER/NO and DETA/NO. Cancer cell lines were cultured with different concentrations of NO donors. The cytotoxic, pro-apoptotic activity of NO donors and their impact on the phosphorylation status of STAT-3 and AKT in cells were determined. The expression of VEGF-A, MMPs and TGF-β was also evaluated.
NO donors inhibited ovarian cancer cells growth making them also more susceptible to the cisplatin cytotoxic activity. Moreover, both NO donors induced apoptosis of cells and decreased activity of signaling proteins (STAT3 and AKT). Similarly, SPER/NO and DETA/NO lowered the secretion of pro-metastatic factors, responsible for cancer cells invasiveness.
The obtained results show that both NO donors demonstrated a wide range of action on both ovarian cancer cell lines. Therefore, they have a high potential of being a supporting compounds in the cancer therapies.
尽管传统的抗卵巢癌疗法有了显著的进步，但肿瘤细胞对各种细胞抑制剂的耐药性仍然是一个相关的问题。因此，新的癌症治疗策略正在被开发。在许多被研究具有潜在抗癌活性的药物中，最有前途的是一氧化氮（NO）供体——合成化合物，它们在体内和/或体外释放 NO。
我们评估了 NO 供体对 SK-OV-3 和 OVCAR-3 卵巢癌细胞系的影响。我们评估了一些癌细胞的特定特征：不受控制的增殖、特定信号蛋白的过度激活、对治疗的高度耐药性以及侵袭性/转移性因子的高表达和分泌。
使用了 NONOates 家族的两个成员：SPER/NO 和 DETA/NO。用不同浓度的 NO 供体培养癌细胞系。测定了 NO 供体的细胞毒性、促凋亡活性及其对细胞中 STAT-3 和 AKT 磷酸化状态的影响。还评估了 VEGF-A、MMPs 和 TGF-β 的表达。
NO 供体抑制卵巢癌细胞生长，使它们对顺铂的细胞毒性更敏感。此外，两种 NO 供体都诱导了细胞凋亡，并降低了信号蛋白（STAT3 和 AKT）的活性。同样，SPER/NO 和 DETA/NO 降低了负责癌细胞侵袭性的促转移因子的分泌。
所得结果表明，两种 NO 供体对两种卵巢癌细胞系均表现出广泛的作用。因此，它们具有成为癌症治疗辅助化合物的高潜力。
