Department of Comparative Endocrinology, Medical University of Lodz, Zeligowskiego 7/9, 90-752 Lodz, Poland.
Department of Cell Cultures and Genomic Analysis, Medical University of Lodz, Zeligowskiego 7/9, 90-752 Lodz, Poland.
Int J Mol Sci. 2021 Dec 21;23(1):52. doi: 10.3390/ijms23010052.
High-grade serous ovarian carcinoma (HGSOC) is the most frequent and malignant form of ovarian cancer. A local renin-angiotensin system (RAS) has been found in the ovary, and changes in selected components of this system were observed in pathological states and also in ovarian cancer. In the present study, we examined the effect of three peptides, Ang-(1-7), Ang-(1-9) and Ang-(3-7), on proliferation and motility of the OVPA8 cell line, a new well-defined and preclinical model of HGSOC. We confirmed the presence of mRNA for all angiotensin receptors in the tested cells. Furthermore, our findings indicate that all tested angiotensin peptides increased the metabolic serum in the medium by activation of cell defense mechanisms such as nuclear factor kappaB signaling pathway andapoptosis. Moreover, tested angiotensin peptides intensified serum starvation-induced cell cycle arrest at the G0/G1 phase. In the case of Ang-(3-7), a significant decrease in the number of Ki67 positive cells (Ki67+) and reduced percentage of activated ERK1/2 levels in ovarian cancer cells were additionally reported. The angiotensin-induced effect of the accumulation of cells in the G0/G1 phase was not observed in OVPA8 cells growing on the medium with 10% FBS. Moreover, in the case of Ang-(3-7), the tendency was quite the opposite. Ang-(1-7) but not Ang-(1-9) or Ang-(3-7) increased the mobility of reluctant-to-migrate OVAP8 cells cultured in the serum-free medium. In any cases, the changes in the expression of and gene, associated with epithelial-mesenchymal transition (EMT), were not observed. In conclusion, we speculate that the adaptation to starvation in nutrient-deprived tumors can be modulated by peptides from the renin-angiotensin system. The influence of angiotensin peptides on cancer cells is highly dependent on the availability of growth factors and nutrients.
高级别浆液性卵巢癌（HGSOC）是最常见和恶性的卵巢癌形式。在卵巢中发现了局部肾素-血管紧张素系统（RAS），并且在病理状态下和在卵巢癌中观察到该系统的选定成分发生变化。在本研究中，我们研究了三种肽（Ang-（1-7）、Ang-（1-9）和 Ang-（3-7））对 OVPA8 细胞系（一种新的明确和临床前的 HGSOC 模型）增殖和运动的影响。我们证实了测试细胞中所有血管紧张素受体的 mRNA 存在。此外，我们的研究结果表明，所有测试的血管紧张素肽通过激活核因子 kappaB 信号通路和细胞凋亡等细胞防御机制，增加了培养基中的代谢血清。此外，测试的血管紧张素肽加剧了血清饥饿诱导的细胞周期停滞在 G0/G1 期。在 Ang-（3-7）的情况下，还报告了卵巢癌细胞中 Ki67 阳性细胞（Ki67+）的数量减少和激活的 ERK1/2 水平降低。在含有 10% FBS 的培养基中生长的 OVPA8 细胞中未观察到血管紧张素诱导的细胞在 G0/G1 期积累的作用。此外，在 Ang-（3-7）的情况下，趋势恰恰相反。Ang-（1-7）但不是 Ang-（1-9）或 Ang-（3-7）增加了在无血清培养基中培养的迁移困难的 OVAP8 细胞的迁移能力。在任何情况下，都未观察到与上皮-间充质转化（EMT）相关的基因和基因的表达变化。总之，我们推测营养剥夺肿瘤中的饥饿适应可以通过肾素-血管紧张素系统的肽来调节。血管紧张素肽对癌细胞的影响高度依赖于生长因子和营养物质的可用性。
