Iaquinta Maria Rosa, De Pace Raffaella, Benkhalqui Assia, Pesaresi Cecilia, Patergnani Simone, Righes Giulio, Pinton Paolo, Tognon Mauro, Martini Fernanda, Mazzoni Elisa
Department of Medical Sciences, Laboratories of Cell Biology and Molecular Genetics, University of Ferrara, Ferrara, Italy.
Department of Translational Medicine, University of Ferrara, Ferrara, Italy.
FASEB J. 2025 Oct 31;39(20):e71120. doi: 10.1096/fj.202500657RR.
Pleural Mesothelioma (PM) is an aggressive tumor with a poor prognosis and limited therapeutic options. Despite the notion that resveratrol (RSV) significantly inhibits the growth of PM cancer cells, it is necessary to evaluate the effects of this stilbene as a tumor suppressor agent. In this work, the effects of the natural polyphenol were investigated on PM cell lines (MSTO-211H and IST-MES 2) to evaluate its action as a potential adjuvant agent, together with chemotherapy. Our results showed that RSV treatment was effective in PM cell lines, in particular in MSTO-211H. RES treatment decreases the viability evaluated with the MTT assay and Live/Dead staining. RSV stimulates the apoptotic process with positive staining for Annexin V-PI and Caspase-3/7 and inhibits the migration ability of both PM cell lines. In IST-MES 2, RSV causes a reduction in mitochondrial and cytoplasmic calcium levels. Moreover, RSV affects cellular morphology, E-cadherin protein expression, and decreased nuclear localization of β-catenin, attenuating Wnt/β-catenin signaling, which regulates tumor cell proliferation. At the molecular level, RSV modulated the expression of key genes that play an important role in cellular adhesion, proliferation, and metabolic activity, as well as AMPK signaling. RSV seems to be a promising therapeutic adjuvant agent for PM treatment.
胸膜间皮瘤（PM）是一种侵袭性肿瘤，预后较差且治疗选择有限。尽管白藜芦醇（RSV）能显著抑制PM癌细胞的生长，但仍有必要评估这种芪类化合物作为肿瘤抑制药物的效果。在本研究中，我们研究了这种天然多酚对PM细胞系（MSTO-211H和IST-MES 2）的影响，以评估其作为潜在辅助药物与化疗联合使用的作用。我们的结果表明，RSV处理对PM细胞系有效，尤其是对MSTO-211H细胞系。RSV处理降低了通过MTT法和活/死染色评估的细胞活力。RSV通过膜联蛋白V-碘化丙啶和半胱天冬酶-3/7阳性染色刺激凋亡过程，并抑制两种PM细胞系的迁移能力。在IST-MES 2细胞系中，RSV导致线粒体和细胞质钙水平降低。此外，RSV影响细胞形态、E-钙黏蛋白的蛋白表达，并降低β-连环蛋白的核定位，减弱Wnt/β-连环蛋白信号传导，该信号传导调节肿瘤细胞增殖。在分子水平上，RSV调节了在细胞黏附、增殖和代谢活性以及AMPK信号传导中起重要作用的关键基因的表达。RSV似乎是一种有前途的PM治疗辅助药物。
