Combined oridonin with cetuximab treatment shows synergistic anticancer effects on laryngeal squamous cell carcinoma: Involvement of inhibition of EGFR and activation of reactive oxygen species-mediated JNK pathway

被引：30
作者：
Cao, Shijie [1 ,2 ]
Xia, Meijuan [1 ]
Mao, Yiwei [1 ,2 ]
Zhang, Qiang [2 ]
Donkor, Paul Owusu [3 ,4 ]
Qiu, Feng [1 ,3 ,4 ]
Kang, Ning [2 ]
机构：
[1] Shenyang Pharmaceut Univ, Key Lab Struct Based Drug Design & Discovery, Sch Tradit Chinese Mat Med, Dept Nat Prod Chem,Minist Educ, Shenyang 110016, Liaoning, Peoples R China
[2] Tianjin Univ Tradit Chinese Med, Sch Integrat Med, Tianjin 300193, Peoples R China
[3] Tianjin State Key Lab Modern Chinese Med, Sch Chinese Mat Med, Tianjin 300193, Peoples R China
[4] Tianjin Univ Tradit Chinese Med, Tianjin 300193, Peoples R China
来源：
INTERNATIONAL JOURNAL OF ONCOLOGY | 2016年 / 49卷 / 05期
基金：
中国博士后科学基金; 中国国家自然科学基金;
关键词：
cetuximab; oridonin; epidermal growth factor receptor; laryngeal squamous cell carcinoma; synergistic anticancer effects; ROS-mediated JNK pathway; GROWTH-FACTOR RECEPTOR; G(2)/M PHASE ARREST; BREAST-CANCER CELLS; INDUCED APOPTOSIS; MONOCLONAL-ANTIBODY; IN-VITRO; COLORECTAL-CANCER; NECK-CANCER; P38; MAPK; KAPPA-B;
D O I：
10.3892/ijo.2016.3696
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Epidermal growth factor receptor (EGFR), a trans membrane glycoprotein, is expressed at high levels in a large proportion of laryngeal squamous cell carcinoma (LSCC). Cetuximab (Cet), an anti-EGFR monoclonal antibody, has limited clinical outcome for patients with head and neck squamous cell carcinoma. Our previous studies showed that oridonin (ORI), a natural and safe kaurene diterpenoid isolated from Rabdosia rubescens, inhibited cell growth in HEp-2 cells through inhibition of EGFR phosphorylation. The aim of the present study was to determine whether ORI could improve the anticancer efficacy of Cet on LSCC. We observed that the combination with Cet and ORI synergistically inhibited cell growth associated with Fas-mediated apoptosis and G2/M phase arrest in two LSCC cell lines (HEp-2 and Tu212 cells). Moreover, combination treatment caused cell death associated with suppression of p-EGFR and activation of reactive oxygen species (ROS)-mediated JNK pathway. In nude mice bearing HEp-2 xenografts, ORI plus Cet caused a significant tumor regression through induction of apoptosis and inhibition of proliferation with no side-effect. Together, our findings suggest that the combination of ORI and Cet has the potential to enhance tumor responses and may significantly improve therapeutic outcomes in LSCC.
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收藏
页码：2075 / 2087
页数：13
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