In cancer treatment, multi-target approach has paid attention to a reasonable strategy for the potential agents. We investigated whether (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol (MMPP) could exert an anticancer effect by dual-regulating VEGFR2 and PPARγ. MMPP showed modulating effects in TNBC type (MDA-MB-231 and MDA-MB-468) and luminal A type (MCF7) breast cancer cell lines. MMPP enhanced PPARγ transcriptional activity and inhibited VEGFR2 phosphorylation. MMPP-induced signaling by VEGFR2 and PPARγ ultimately triggered the downregulation of AKT activity. MMPP exhibited anticancer effects, as evidenced by growth inhibition, inducement of apoptosis, and suppression of migration and invasion. At the molecular level, MMPP activated pro-apoptotic proteins (caspase3, caspase8, caspase9, and bax), while inhibiting the anti-apoptotic proteins (bcl2). Additionally, MMPP inhibited the mRNA expressions of EMT-promoting transcription factors. Therefore, our findings showed molecular mechanisms of MMPP by regulating VEGFR2 and PPARγ, and suggested that MMPP has potential to treat breast cancer.

中文翻译：

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(E)-2-甲氧基-4-(3-(4-甲氧基苯基) Prop-1-en-1-yl) 苯酚通过双重调节 VEGFR2 和 PPARγ 抑制乳腺癌进展。

在癌症治疗中，多靶点方法注重针对潜在药物的合理策略。我们研究了(E)-2-甲氧基-4-(3-(4-甲氧基苯基)丙-1-en-1-基)苯酚(MMPP)是否可以通过双重调节VEGFR2和PPARγ发挥抗癌作用。MMPP 在 TNBC 型（MDA-MB-231 和 MDA-MB-468）和 luminal A 型（MCF7）乳腺癌细胞系中显示出调节作用。MMPP 增强 PPARγ 转录活性并抑制 VEGFR2 磷酸化。VEGFR2 和 PPARγ 诱导的 MMPP 信号传导最终引发 AKT 活性的下调。MMPP 具有抗癌作用，如生长抑制、诱导细胞凋亡以及抑制迁移和侵袭。在分子水平上，MMPP 激活促凋亡蛋白（caspase3、caspase8、caspase9 和 bax），同时抑制抗凋亡蛋白 (bcl2)。此外，MMPP 抑制 EMT 促进转录因子的 mRNA 表达。因此，我们的研究结果揭示了MMPP通过调节VEGFR2和PPARγ的分子机制，并表明MMPP具有治疗乳腺癌的潜力。