Department of Pharmacology, Hainan Medical College, Haikou, Hainan, China.
Bull Exp Biol Med. 2022 Jun;173(2):240-245. doi: 10.1007/s10517-022-05526-y. Epub 2022 Jun 23.
This study aims to understand the molecular basis of manganese superoxide dismutase (MnSOD) impacts on breast cancer cell growth. Modulation of the level of MnSOD by genetic engineering led significant changes in the expression of angiopoietin-like protein 4 (ANGPTL4) and activity of peroxisome proliferator-activated receptor α (PPARα) in MCF7 cells. PPARα agonist increased ANGPTL4 expression inhibited by MnSOD. Proliferation of MCF7 cells was inhibited by MnSOD, however, ANGPTL4 transduction into MCF7 cells with MnSOD overexpression significantly stimulated cell proliferation. MnSOD induced G0/G1 cell cycle arrest, nevertheless, ANGPTL4 transduction significantly reduced the percentage of cells in G0/G1 phase overexpressing MnSOD. In conclusion, MnSOD suppressed the expression of ANGPTL4 in breast cancer cells via the PPARα signaling pathway, and ANGPTL4 was involved in MnSOD-mediated proliferation inhibition and cell cycle arrest.
本研究旨在探讨锰超氧化物歧化酶(MnSOD)对乳腺癌细胞生长影响的分子基础。通过基因工程调节 MnSOD 的水平,导致 MCF7 细胞中血管生成素样蛋白 4(ANGPTL4)的表达和过氧化物酶体增殖物激活受体 α(PPARα)的活性发生显著变化。PPARα 激动剂增加了 MnSOD 抑制的 ANGPTL4 的表达。MnSOD 抑制 MCF7 细胞的增殖,然而,MnSOD 过表达转导 ANGPTL4 到 MCF7 细胞中显著刺激细胞增殖。MnSOD 诱导 G0/G1 细胞周期停滞,但 ANGPTL4 转导显著降低了过表达 MnSOD 的细胞中处于 G0/G1 期的百分比。总之,MnSOD 通过 PPARα 信号通路抑制乳腺癌细胞中 ANGPTL4 的表达,而 ANGPTL4 参与了 MnSOD 介导的增殖抑制和细胞周期停滞。