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穿心莲内酯通过上调磷酸化p53在体外和体内增强顺铂对人口腔鳞状细胞癌的抗肿瘤作用。

Anti-tumor effect of cisplatin in human oral squamous cell carcinoma was enhanced by andrographolide via upregulation of phospho-p53 in vitro and in vivo.

作者信息

Chen Songjie, Hu Hui, Miao Shushu, Zheng Jiayong, Xie Zhijian, Zhao Hui

机构信息

1 Department of Stomatology, Wenzhou People's Hospital, Wenzhou, China.

2 Oral and Maxillofacial Surgery, Affiliated Hospital for Stomatology of Zhejiang University School of Medicine, Hangzhou, China.

出版信息

Tumour Biol. 2017 May;39(5):1010428317705330. doi: 10.1177/1010428317705330.

DOI:10.1177/1010428317705330
PMID:28513299
Abstract

Oral squamous cell carcinoma is one of the most common neoplasm in the world. Despite the improvements in diagnosis and treatment, the outcome is still poor now. Thus, the development of novel therapeuticapproaches is needed. The aim of this study is to assess the synergistic anti-tumor effect of andrographolide with cisplatin (DDP) in oral squamous cell carcinoma CAL-27 cells in vitro and in vivo. We performed Cell Counting Kit-8 proliferation assay, apoptosis assay, and western blotting on CAL-27 cells treated with andrographolide, DDP or the combination in vitro. In vivo, we also treated CAL-27 xenografts with andrographolide or the combination, and performed terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay and immunohistochemical analysis of Ki-67. The results showed the combination of andrographolide and DDP synergistically inhibited CAL-27 cell proliferation in vitro and caused tumor regression in vivo in the CAL-27 xenografts. In addition, the synergistic anti-tumor effect of andrographolide with synergistic was due to an enhanced apoptosis. Moreover, the combination therapy upregulated the expression level of p-p53 in vitro and decreased Ki-67 expression in vivo. Our data indicate that the combination treatment of andrographolide and DDP results in synergistic anti-tumor growth activity against oral squamous cell carcinoma CAL-27 in vitro and in vivo. These results demonstrated that combination of andrographolide with DDP was likely to represent a potential therapeutic strategy for oral squamous cell carcinoma.

摘要

口腔鳞状细胞癌是世界上最常见的肿瘤之一。尽管在诊断和治疗方面有所改进,但目前的治疗效果仍然不佳。因此,需要开发新的治疗方法。本研究的目的是评估穿心莲内酯与顺铂(DDP)在体外和体内对口腔鳞状细胞癌CAL-27细胞的协同抗肿瘤作用。我们对体外经穿心莲内酯、DDP或两者联合处理的CAL-27细胞进行了细胞计数试剂盒-8增殖试验、凋亡试验和蛋白质印迹分析。在体内,我们还用穿心莲内酯或两者联合处理CAL-27异种移植瘤,并进行了末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记试验和Ki-67免疫组化分析。结果表明,穿心莲内酯与DDP联合使用在体外协同抑制CAL-27细胞增殖,并在体内使CAL-27异种移植瘤发生肿瘤消退。此外,穿心莲内酯的协同抗肿瘤作用是由于凋亡增强。而且,联合治疗在体外上调了p-p53的表达水平,在体内降低了Ki-67的表达。我们的数据表明,穿心莲内酯与DDP联合治疗在体外和体内均对口腔鳞状细胞癌CAL-27具有协同抗肿瘤生长活性。这些结果表明,穿心莲内酯与DDP联合使用可能是口腔鳞状细胞癌的一种潜在治疗策略。

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