PMID- 27667173
OWN - NLM
STAT- MEDLINE
DCOM- 20170713
LR  - 20181202
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Linking)
VI  - 49
IP  - 5
DP  - 2016 Nov
TI  - 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.
PG  - 2075-2087
LID - 10.3892/ijo.2016.3696 [doi]
AB  - Epidermal growth factor receptor (EGFR), a transmembrane 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.
FAU - Cao, Shijie
AU  - Cao S
AD  - Department of Natural Products Chemistry, School of Traditional Chinese Materia 
      Medica, Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of 
      Education, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, P.R. 
      China.
FAU - Xia, Meijuan
AU  - Xia M
AD  - Department of Natural Products Chemistry, School of Traditional Chinese Materia 
      Medica, Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of 
      Education, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, P.R. 
      China.
FAU - Mao, Yiwei
AU  - Mao Y
AD  - Department of Natural Products Chemistry, School of Traditional Chinese Materia 
      Medica, Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of 
      Education, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, P.R. 
      China.
FAU - Zhang, Qiang
AU  - Zhang Q
AD  - School of Integrative Medicine, Tianjin University of Traditional Chinese 
      Medicine, Tianjin 300193, P.R. China.
FAU - Donkor, Paul Owusu
AU  - Donkor PO
AD  - School of Chinese Materia Medica, Tianjin State Key Laboratory of Modern Chinese 
      Medicine and Tianjin University of Traditional Chinese Medicine, Tianjin 300193, 
      P.R. China.
FAU - Qiu, Feng
AU  - Qiu F
AD  - Department of Natural Products Chemistry, School of Traditional Chinese Materia 
      Medica, Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of 
      Education, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, P.R. 
      China.
FAU - Kang, Ning
AU  - Kang N
AD  - School of Integrative Medicine, Tianjin University of Traditional Chinese 
      Medicine, Tianjin 300193, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20160919
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (Diterpenes, Kaurane)
RN  - 0 (Reactive Oxygen Species)
RN  - 0APJ98UCLQ (oridonin)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 4)
RN  - PQX0D8J21J (Cetuximab)
SB  - IM
MH  - Animals
MH  - Antineoplastic Combined Chemotherapy Protocols/*pharmacology
MH  - Apoptosis/drug effects
MH  - Blotting, Western
MH  - Carcinoma, Squamous Cell/drug therapy/metabolism/*pathology
MH  - Cell Proliferation/drug effects
MH  - Cetuximab/administration & dosage
MH  - Diterpenes, Kaurane/administration & dosage
MH  - *Drug Synergism
MH  - ErbB Receptors/*antagonists & inhibitors/metabolism
MH  - Female
MH  - Flow Cytometry
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Laryngeal Neoplasms/drug therapy/metabolism/*pathology
MH  - MAP Kinase Kinase 4/*metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Microscopy, Fluorescence
MH  - Reactive Oxygen Species/*metabolism
MH  - Tumor Cells, Cultured
MH  - Xenograft Model Antitumor Assays
EDAT- 2016/10/26 06:00
MHDA- 2017/07/14 06:00
CRDT- 2016/09/27 06:00
PHST- 2016/06/13 00:00 [received]
PHST- 2016/08/30 00:00 [accepted]
PHST- 2016/10/26 06:00 [pubmed]
PHST- 2017/07/14 06:00 [medline]
PHST- 2016/09/27 06:00 [entrez]
AID - 10.3892/ijo.2016.3696 [doi]
PST - ppublish
SO  - Int J Oncol. 2016 Nov;49(5):2075-2087. doi: 10.3892/ijo.2016.3696. Epub 2016 Sep 
      19.