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奥昔辛对肝细胞癌的抗肿瘤作用。

Antitumoral effect of Ocoxin in hepatocellular carcinoma.

作者信息

Díaz-Rodríguez Elena, El-Mallah Al-Mahy, Sanz Eduardo, Pandiella Atanasio

机构信息

Institute of Molecular and Cellular Cancer Biology, CSIC-University of Salamanca, 37007 Salamanca, Spain.

Catalysis, S.L., 28016 Madrid, Spain.

出版信息

Oncol Lett. 2017 Aug;14(2):1950-1958. doi: 10.3892/ol.2017.6440. Epub 2017 Jun 21.

Abstract

Hepatocellular carcinoma (HCC) is becoming one of the most prevalent types of cancer worldwide. The most efficient types of treatment at present include surgical resection and liver transplantation, but these treatments may only be used in a small percentage of patients. In order to identify novel therapeutic strategies for this disease, the present study explored the potential antitumoral effect of Ocoxin® oral solution (OOS) in HCC. OOS inhibited the proliferation of HCC cell lines in a time- and dose-dependent manner, being more efficient when used in combination with sorafenib, a standard of care treatment for patients diagnosed with advanced-stage disease. Mechanistic studies indicated that the effect of OOS was due to the induction of cell cycle arrest rather than the stimulation of apoptotic cell death. The cell cycle was slowed down in all phases in the HCC cell lines treated with OOS. Finally, when tested in animal models of HCC, OOS reduced tumor progression through the induction of necrosis in xenograft tumor models. Considering the poor prognosis and high resistance to antitumor treatments of HCC, the antiproliferative action of OOS, particularly in combination with sorafenib, provides the opportunity to investigate the effect of combined therapy in a clinical setting.

摘要

肝细胞癌(HCC)正成为全球最常见的癌症类型之一。目前最有效的治疗方法包括手术切除和肝移植,但这些治疗方法可能仅适用于一小部分患者。为了确定针对这种疾病的新型治疗策略,本研究探讨了奥克辛®口服溶液(OOS)在HCC中的潜在抗肿瘤作用。OOS以时间和剂量依赖性方式抑制HCC细胞系的增殖,与索拉非尼联合使用时效果更佳,索拉非尼是诊断为晚期疾病患者的标准治疗药物。机制研究表明,OOS的作用是由于诱导细胞周期停滞而非刺激凋亡性细胞死亡。在用OOS处理的HCC细胞系中,细胞周期在所有阶段均减慢。最后,当在HCC动物模型中进行测试时,OOS通过诱导异种移植肿瘤模型中的坏死来降低肿瘤进展。考虑到HCC预后不良且对抗肿瘤治疗的高抗性,OOS的抗增殖作用,特别是与索拉非尼联合使用时,为在临床环境中研究联合治疗的效果提供了机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a065/5530179/379947825e53/ol-14-02-1950-g00.jpg

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