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羊膜间充质基质细胞条件培养基与紫杉醇联合对二维和三维体外模型中卵巢癌细胞活力和迁移的协同作用

Synergistic Effect of Conditioned Medium from Amniotic Membrane Mesenchymal Stromal Cells Combined with Paclitaxel on Ovarian Cancer Cell Viability and Migration in 2D and 3D In Vitro Models.

作者信息

Chiodelli Paola, Bonassi Signoroni Patrizia, Scalvini Elisa, Farigu Serafina, Giuzzi Elisabetta, Paini Alice, Papait Andrea, Stefani Francesca Romana, Silini Antonietta Rosa, Parolini Ornella

机构信息

Department of Life Science and Public Health, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.

Centro di Ricerca E. Menni, Fondazione Poliambulanza Istituto Ospedaliero, 25124 Brescia, Italy.

出版信息

Pharmaceutics. 2025 Mar 26;17(4):420. doi: 10.3390/pharmaceutics17040420.

Abstract

Ovarian cancer accounts for more deaths than any other cancer of the female reproductive system. Despite standard care, recurrence due to tumor spread and chemoresistance is common, highlighting the need for novel therapies. Mesenchymal stromal cells from the human amniotic membrane (hAMSC) and the intact amniotic membrane (hAM) are promising due to their secretion of tumor-modulating bioactive factors, accessibility from biological waste, and ethical favorability. Furthermore, unlike isolated cells, hAM provides an easier, clinically translatable product. We previously demonstrated that hAMSC can inhibit tumor cell proliferation, both in contact and transwell settings, suggesting that hAMSC secrete bioactive factors able to target tumor cells. This study evaluates the anti-tumor effects of bioactive factors from hAMSC and hAM conditioned medium (CM) on ovarian cancer cells in 2D and 3D models, alone or with paclitaxel. The impact of CM, alone or with paclitaxel, was tested on ovarian cancer cell proliferation, migration, invasion, and on angiogenesis. hAMSC-CM and hAM-CM inhibited the proliferation and migration in 2D cultures and reduced spheroid growth and invasion in 3D models. Combining CM with paclitaxel enhanced anti-tumor effects in both settings. hAMSC-CM and hAM-CM show therapeutic potential against ovarian cancer, with synergistic benefits when combined with paclitaxel.

摘要

卵巢癌导致的死亡人数超过女性生殖系统的任何其他癌症。尽管有标准治疗方法,但由于肿瘤扩散和化疗耐药导致的复发很常见,这凸显了对新型疗法的需求。来自人羊膜的间充质基质细胞(hAMSC)和完整羊膜(hAM)很有前景,因为它们能分泌调节肿瘤的生物活性因子,可从生物废弃物中获取,且符合伦理要求。此外,与分离的细胞不同,hAM提供了一种更易于临床转化的产品。我们之前证明,hAMSC在接触和Transwell实验中均能抑制肿瘤细胞增殖,这表明hAMSC分泌能够靶向肿瘤细胞的生物活性因子。本研究评估了hAMSC和hAM条件培养基(CM)中的生物活性因子在二维和三维模型中对卵巢癌细胞的抗肿瘤作用,单独使用或与紫杉醇联合使用。测试了CM单独或与紫杉醇联合使用对卵巢癌细胞增殖、迁移、侵袭和血管生成的影响。hAMSC-CM和hAM-CM在二维培养中抑制了增殖和迁移,并在三维模型中减少了球体生长和侵袭。在两种情况下,将CM与紫杉醇联合使用均可增强抗肿瘤作用。hAMSC-CM和hAM-CM对卵巢癌显示出治疗潜力,与紫杉醇联合使用时具有协同效益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e05d/12030038/e0cdccde72a7/pharmaceutics-17-00420-g001.jpg

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