Department of Hormones, Medical Research Division, National Research Centre, Dokki, Cairo, Egypt.
Department of Chemistry, Faculty of Science, Cairo University, Cairo, Egypt.
Asian Pac J Cancer Prev. 2021 Mar 1;22(3):819-826. doi: 10.31557/APJCP.2021.22.3.819.
Progesterone derivatives have explored an improved effect on human cancer cells through combination of the explored heterocycles with progesterone moiety.miRNAs have an important role in moderating cancer cell survival, proliferation and drug resistance. The current study tested the hypothesis "whether miR-34a inhibitor has a negative impact on apoptosis and angiogenesis in MCF-7 cells treated with newly synthesized progesterone derivatives".
MCF-7 cells were treated with progesterone derivatives individually and in combination with miR-34a inhibitor. miR-34a expression levels were measured in MCF-7 cells treated with progesterone derivatives using QRT-PCR. MCF-7 cells treated with progesterone derivatives individually showed increased miR-34a expression levels. miR-34a deficient cells were treated with the newly synthesized progesterone derivatives, after that, apoptotic and angiogenic gene expression levels were determined using QRT-PCR. The studied genes were as follows: apoptotic (Bcl-2, survivin, CCND1, CDC2, P53 and P21) and angiogenic (VEGF, Hif-1α, MMP-2, Ang-1, Ang-2, and FGF-1).
The results showed that miR-34a deficient MCF-7 cells treated with the newly progesterone derivatives still have promising effects on apoptotic and angiogenic genes. Besides, results revealed that miRNA-34a deficient MCF-7 cells exhibited improved effect of tested compounds in some apoptotic and angiogenic genes such as CDC-2, MMP-2.
These results revealed that miR-34a inhibitor did not have remarkable negative effect on apoptosis and angiogenesis. On contrary, it showed an improved effect on some genes. And consequently, miR-34a inhibitor could be used safely as a tool to tackle drug resistance in breast cancer cells.
通过将探索的杂环与孕酮部分结合，孕酮衍生物探索了对人类癌细胞的改善作用。miRNAs 在调节癌细胞存活、增殖和耐药性方面发挥着重要作用。本研究检验了“miR-34a 抑制剂是否对 MCF-7 细胞中用新合成的孕酮衍生物处理的细胞凋亡和血管生成有负面影响”这一假说。
MCF-7 细胞分别用孕酮衍生物和 miR-34a 抑制剂处理。用 QRT-PCR 测量用孕酮衍生物处理的 MCF-7 细胞中的 miR-34a 表达水平。单独用孕酮衍生物处理的 MCF-7 细胞显示 miR-34a 表达水平增加。用新合成的孕酮衍生物处理 miR-34a 缺陷细胞，然后用 QRT-PCR 测定凋亡和血管生成基因的表达水平。研究的基因如下：凋亡（Bcl-2、survivin、CCND1、CDC2、P53 和 P21）和血管生成（VEGF、Hif-1α、MMP-2、Ang-1、Ang-2 和 FGF-1）。
结果表明，用新孕酮衍生物处理的 miR-34a 缺陷 MCF-7 细胞仍对凋亡和血管生成基因有明显的作用。此外，结果表明，miR-34a 缺陷 MCF-7 细胞在一些凋亡和血管生成基因（如 CDC-2、MMP-2）中表现出测试化合物的改善作用。
这些结果表明，miR-34a 抑制剂对细胞凋亡和血管生成没有显著的负作用。相反，它对一些基因显示出了改善作用。因此，miR-34a 抑制剂可以安全地用作克服乳腺癌细胞耐药性的工具。
