Department of Otolaryngology - Head and Neck Surgery, Tri-Service General Hospital, National Defense Medical Center, Taiwan.
Department of Otolaryngology, Taitung Mackay Memorial Hospital, Taiwan.
Phytomedicine. 2019 Mar 15;56:269-278. doi: 10.1016/j.phymed.2018.05.007. Epub 2018 May 8.
Treatment for metastatic nasopharyngeal carcinoma (NPC) is challenging. Till now, a truly effective chemotherapy regimen for NPC has not yet been identified. These clinical observations prompted us to investigate a potential drug as alternative option for treating.
This study evaluated the inhibitory effects of Ovatodiolide (Ova), on tumorigenic and cancer stem cell characteristics of NPC cells.
Two NPC cell lines (NPC-BM1 and NPC-BM2) were used to examine the anticancer effects of Ova and the molecular mechanism underlying these activities by using sulforhodamine B cytotoxicity assay, western blot, immunofluorescence, migration, colony and tumorsphere formation assays.
Ova significantly inhibited the viability of BM1 and BM2 cells, downregulated Bcl-xL and Puma, and upregulated Bax/Bad expression levels. Ova dose-dependent suppressed migratory/invasive potential of NPC cells, and reduced ability to form colonies. Ova-induced apoptosis correlated with increased Bax/Bcl-xL ratio while NPC motility and colony formation inhibition were associated with reduced expression of p-FAK, p-PXN, F-actin, and Slug proteins and increased E-cadherin. Furthermore, ova inhibited NPC tumorsphere formation, associated with decreased SOX2, OCT4 and JAK-STAT signaling pathway. Ova also attenuated NPC stem cell tumorigenicity, inhibited tumor growth, and enhanced the sensitivity of NPC cells to cisplatin treatment, in vivo.
Our results demonstrated the anticancer efficacy of Ova in NPC and its potential as a putative inhibitor of JAK2 and STAT3, which are essential in tumorigenesis of NPC. Further development of Ova is encouraged.
转移性鼻咽癌（NPC）的治疗具有挑战性。到目前为止，尚未发现针对 NPC 的真正有效的化疗方案。这些临床观察促使我们研究一种潜在的药物作为治疗的替代选择。
本研究评估了 Ovatodiolide（Ova）对 NPC 细胞致瘤性和癌症干细胞特性的抑制作用。
使用 NPC-BM1 和 NPC-BM2 两种 NPC 细胞系，通过磺酰罗丹明 B 细胞毒性测定、western blot、免疫荧光、迁移、集落和肿瘤球形成测定来检测 Ova 的抗癌作用及其作用机制。
Ova 显著抑制 BM1 和 BM2 细胞的活力，下调 Bcl-xL 和 Puma，并上调 Bax/Bad 表达水平。Ova 呈剂量依赖性抑制 NPC 细胞的迁移/侵袭潜能，并降低集落形成能力。Ova 诱导的细胞凋亡与 Bax/Bcl-xL 比值增加相关，而 NPC 运动和集落形成抑制与 p-FAK、p-PXN、F-actin 和 Slug 蛋白表达降低以及 E-cadherin 增加相关。此外，ova 抑制 NPC 肿瘤球形成，与 Sox2、OCT4 和 JAK-STAT 信号通路的减少有关。Ova 还减弱了 NPC 干细胞的致瘤性，抑制了肿瘤生长，并增强了 NPC 细胞对顺铂治疗的敏感性，在体内。
我们的研究结果表明，Ova 在 NPC 中的抗癌疗效及其作为 JAK2 和 STAT3 的潜在抑制剂的潜力，这在 NPC 的肿瘤发生中是必不可少的。鼓励进一步开发 Ova。
