PMID- 30430397
OWN - NLM
STAT- MEDLINE
DCOM- 20200420
LR  - 20211115
IS  - 1573-675X (Electronic)
IS  - 1360-8185 (Linking)
VI  - 24
IP  - 1-2
DP  - 2019 Feb
TI  - Molecular mechanisms of apoptosis and autophagy elicited by combined treatment 
      with oridonin and cetuximab in laryngeal squamous cell carcinoma.
PG  - 33-45
LID - 10.1007/s10495-018-1497-0 [doi]
AB  - Combined oridonin (ORI), a natural and safe kaurene diterpenoid isolated from 
      Rabdosia rubescens, and cetuximab (Cet), an anti-EGFR monoclonal antibody, have 
      been reported to exert synergistic anti-tumor effects against laryngeal squamous 
      cell carcinoma (LSCC) both in vitro and in vivo by our group. In the present 
      study, we further found that ORI/Cet treatment not only resulted in apoptosis but 
      also induced autophagy. AMPK/mTOR signaling pathway was found to be involved in 
      the activation of autophagy in ORI/Cet-treated LSCC cells, which is independent 
      of p53 status. Additionally, chromatin immunoprecipitation (ChIP) assay showed 
      that ORI/Cet significantly increased the binding NF-kappaB family member p65 with the 
      promotor of BECN 1, and p65-mediated up-regulation of BECN 1 caused by ORI/Cet is 
      coupled to increased autophagy. On the other hand, we demonstrated that either 
      Beclin 1 SiRNA or autophagy inhibitors could increase ORI/Cet induced-apoptosis, 
      indicating that autophagy induced by combination of the two agents plays a 
      cytoprotective role. Interestingly, 48 h after the combined treatment, autophagy 
      began to decrease but apoptosis was significantly elevated. Our findings suggest 
      that autophagy might be strongly associated with the antitumor efficacy of 
      ORI/Cet, which may be beneficial to the clinical application of ORI/Cet in LSCC 
      treatment.
FAU - Cao, Shijie
AU  - Cao S
AD  - Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of 
      Traditional Chinese Medicine, Tianjin, 300193, People's Republic of China.
FAU - Huang, Yiyuan
AU  - Huang Y
AD  - School of Integrative Medicine, Tianjin University of Traditional Chinese 
      Medicine, 312 Anshanxi Road, Tianjin, 300193, People's Republic of China.
AD  - Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of 
      Traditional Chinese Medicine, Tianjin, 300193, People's Republic of China.
FAU - Zhang, Qiang
AU  - Zhang Q
AD  - School of Integrative Medicine, Tianjin University of Traditional Chinese 
      Medicine, 312 Anshanxi Road, Tianjin, 300193, People's Republic of China.
FAU - Lu, Fangjin
AU  - Lu F
AD  - School of Chinese Materia Medica, Tianjin University of Traditional Chinese 
      Medicine, Tianjin, 300193, People's Republic of China.
FAU - Donkor, Paul Owusu
AU  - Donkor PO
AD  - School of Pharmacy, University of Health and Allied Sciences, Ho, PMB 31, Ghana.
FAU - Zhu, Yan
AU  - Zhu Y
AD  - Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of 
      Traditional Chinese Medicine, Tianjin, 300193, People's Republic of China.
FAU - Qiu, Feng
AU  - Qiu F
AD  - School of Chinese Materia Medica, Tianjin University of Traditional Chinese 
      Medicine, Tianjin, 300193, People's Republic of China.
FAU - Kang, Ning
AU  - Kang N
AD  - School of Integrative Medicine, Tianjin University of Traditional Chinese 
      Medicine, 312 Anshanxi Road, Tianjin, 300193, People's Republic of China. 
      kangndd@163.com.
LA  - eng
GR  - 81373797/National Natural Science Foundation of China/International
GR  - 81102855/National Natural Science Foundation of China/International
GR  - 2014T70224/China postdoctoral Science Special Foundation/International
GR  - 2013M541192/China Postdoctoral Science Foundation/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Apoptosis
JT  - Apoptosis : an international journal on programmed cell death
JID - 9712129
RN  - 0 (Diterpenes, Kaurane)
RN  - 0 (Reactive Oxygen Species)
RN  - 0APJ98UCLQ (oridonin)
RN  - PQX0D8J21J (Cetuximab)
SB  - IM
MH  - Animals
MH  - Antineoplastic Combined Chemotherapy 
      Protocols/metabolism/pharmacology/*therapeutic use
MH  - Apoptosis/*drug effects/genetics
MH  - Autophagy/*drug effects/genetics
MH  - Carcinoma, Squamous Cell/*drug therapy/metabolism/pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cetuximab/*administration & dosage/pharmacology
MH  - Diterpenes, Kaurane/*administration & dosage/pharmacology
MH  - Drug Synergism
MH  - Humans
MH  - Laryngeal Neoplasms/*drug therapy/pathology
MH  - Mice
MH  - Mice, Nude
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/drug effects/genetics
MH  - Xenograft Model Antitumor Assays
OTO - NOTNLM
OT  - Apoptosis
OT  - Autophagy
OT  - Cetuximab
OT  - Laryngeal squamous cell carcinoma
OT  - Oridonin
EDAT- 2018/11/16 06:00
MHDA- 2020/04/21 06:00
CRDT- 2018/11/16 06:00
PHST- 2018/11/16 06:00 [pubmed]
PHST- 2020/04/21 06:00 [medline]
PHST- 2018/11/16 06:00 [entrez]
AID - 10.1007/s10495-018-1497-0 [pii]
AID - 10.1007/s10495-018-1497-0 [doi]
PST - ppublish
SO  - Apoptosis. 2019 Feb;24(1-2):33-45. doi: 10.1007/s10495-018-1497-0.