Department of Central Laboratory, Affiliated Hospital of Jining Medical University, Jining, Shandong 272029, P.R. China.
Department of Neurosurgery, Affiliated Hospital of Jining Medical University, Jining, Shandong 272029, P.R. China.
Mol Med Rep. 2021 May;23(5). doi: 10.3892/mmr.2021.11959. Epub 2021 Mar 24.
Corilagin, extracted from the Euphorbiaceae and plants, inhibits the growth of a number of types of tumors. Compared with temozolomide, the traditional chemotherapy drug, corilagin has demonstrated stronger antitumor activity. However, the pharmaceutical mechanism of corilagin in glioma remains unclear. Nuclear factor erythroid 2 like 2 (NFE2L2 or NRF2) is positively associated with several types of tumor including glioma. In the present study, NRF2 expression was higher in glioma tissues compared with non‑glioma specimens. Therefore, it was hypothesized that corilagin targets NRF2 regulation of U251 cell apoptosis. The present study used Hoechst 33258 staining to demonstrate that corilagin induced glioma cell apoptosis and observed that the expression of the apoptosis‑related gene Bcl‑2 was reduced. In addition, corilagin induced autophagy and promoted the conversion of light chain 3 (LC3) protein from LC3Ⅰ to LC3II. NRF2 expression was downregulated by corilagin stimulation. Furthermore, the gene expression pattern following knockdown of NRF2 in U251 cells using siRNA was consistent with corilagin stimulation. Therefore, it was preliminarily concluded that corilagin induces apoptosis and autophagy by reducing NRF2 expression.
鞣花酸是从大戟科和植物中提取的，能抑制多种类型肿瘤的生长。与传统化疗药物替莫唑胺相比，鞣花酸具有更强的抗肿瘤活性。然而，鞣花酸在神经胶质瘤中的药物机制尚不清楚。核因子红细胞 2 样 2（NFE2L2 或 NRF2）与多种肿瘤（包括神经胶质瘤）呈正相关。本研究表明，与非神经胶质瘤标本相比，神经胶质瘤组织中 NRF2 的表达更高。因此，研究假设鞣花酸靶向 NRF2 调节 U251 细胞凋亡。本研究采用 Hoechst 33258 染色证明鞣花酸诱导神经胶质瘤细胞凋亡，并观察到凋亡相关基因 Bcl-2 的表达减少。此外，鞣花酸诱导自噬，并促进轻链 3（LC3）蛋白从 LC3Ⅰ向 LC3Ⅱ的转化。鞣花酸刺激可下调 NRF2 的表达。此外，用 siRNA 敲低 U251 细胞中的 NRF2 后，基因表达模式与鞣花酸刺激一致。因此，初步得出结论，鞣花酸通过降低 NRF2 的表达诱导细胞凋亡和自噬。
