PurposeThis study aimed to clarify whether immunogenic cell death (ICD) contributed to the anti-tumor action of resveratrol against ovarian carcinoma.MethodsResveratrol suppressed cell proliferation and induced apoptosis in ovarian carcinoma cells. In addition, resveratrol treatment stimulated cell surface exposure of calreticulin, HMGB1 secretion and ATP release.ResultsVaccination with resveratrol-pretreated ID8 cells significantly inhibited growth of subsequent inoculated xenograft tumor. Direct administration with resveratrol suppressed tumor progression accompanied with compromised cell proliferation and enhanced cell apoptosis. We further characterized increases of both mature dendritic cells and cytotoxic T cells in xenograft tumor in response to resveratrol treatment, which also inhibited TGF-β production and stimulated both IL12p7 and IFN-γ secretion. Most importantly, we demonstrated that combination with PD-1 antibody greatly inhibited tumor growth, while depletion of CD8+ T cells by neutralizing antibody restored xenograft progression.ConclusionOur data suggested resveratrol exerted anti-tumor action against ovarian cancer via both apoptosis and ICD pathways.

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白藜芦醇诱导人和鼠卵巢癌细胞的免疫原性细胞死亡

目的本研究旨在阐明免疫原性细胞死亡（ICD）是否有助于白藜芦醇对卵巢癌的抗肿瘤作用。方法白藜芦醇抑制卵巢癌细胞增殖并诱导其凋亡。此外，白藜芦醇处理刺激了钙网蛋白的细胞表面暴露、HMGB1分泌和ATP释放。结果白藜芦醇预处理的ID8细胞接种显着抑制随后接种的异种移植肿瘤的生长。白藜芦醇直接给药抑制了肿瘤进展，伴随着受损的细胞增殖和增强的细胞凋亡。我们进一步表征了异种移植肿瘤中成熟树突状细胞和细胞毒性 T 细胞在白藜芦醇治疗后的增加，这也抑制了TGF-β的产生并刺激了IL12p7和IFN-γ的分泌。最重要的是，我们证明了与 PD-1 抗体的组合极大地抑制了肿瘤生长，而通过中和抗体消耗 CD8+ T 细胞恢复了异种移植物的进展。结论我们的数据表明白藜芦醇通过细胞凋亡和 ICD 途径对卵巢癌发挥抗肿瘤作用。