PMID- 31485602
OWN - NLM
STAT- MEDLINE
DCOM- 20200203
LR  - 20200203
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Linking)
VI  - 55
IP  - 4
DP  - 2019 Oct
TI  - Secreted amphiregulin promotes vincristine resistance in oral squamous cell 
      carcinoma.
PG  - 949-959
LID - 10.3892/ijo.2019.4866 [doi]
AB  - Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer. 
      Despite advances in surgery, radiotherapy and chemotherapy, the overall 5‑year 
      survival rate of patients with OSCC has not significantly improved. In addition, 
      the prognosis of patients with advanced‑stage OSCC remains poor. Therefore, it is 
      necessary to develop novel therapeutic modalities. Vincristine (VCR), a naturally 
      occurring vinca alkaloid, is a classical microtubule‑destabilizing agent and is 
      widely used in the treatment of a number of cancers. Despite the proven antitumor 
      benefits of VCR treatment, one of the major reasons for the failure of treatment 
      is drug resistance. Changes in the tumor microenvironment are responsible for 
      cross‑talk between cells, which may facilitate drug resistance in cancers; 
      secreted proteins may promote communication between cancer cells to induce the 
      development of resistance. To identify the secreted proteins involved in VCR 
      resistance, conditioned media was obtained, and an antibody array was conducted 
      to screen a comprehensive secretion profile between VCR‑resistant (SAS‑VCR) and 
      parental (SAS) OSCC cell lines. The results showed that amphiregulin (AREG) was 
      highly expressed and secreted in SAS‑VCR cells. Pretreatment with exogenous 
      recombinant AREG markedly increased drug resistance against VCR in OSCC cells, as 
      assessed by an MTT assay. Colony formation, MTT and western blot assays were 
      performed to investigate the effects of AREG knockdown on VCR sensitivity. The 
      results indicated that AREG expression can regulate VCR resistance in OSCC cells; 
      overexpression of AREG increased VCR resistance in parental cells, whereas AREG 
      knockdown decreased the VCR resistance of resistant cells. In addition, it was 
      also demonstrated that the glycogen synthase kinase‑3beta pathway may be involved in 
      AREG‑induced VCR resistance. These findings may provide rationale to combine VCR 
      with blockade of AREG‑related pathways for the effective treatment of OSCC.
FAU - Hsieh, Ming-Ju
AU  - Hsieh MJ
AD  - Oral Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan, 
      R.O.C.
FAU - Chen, Yin-Hong
AU  - Chen YH
AD  - Department of Otorhinolaryngology‑Head and Neck Surgery, Changhua Christian 
      Hospital, Changhua 500, Taiwan, R.O.C.
FAU - Lee, I-Neng
AU  - Lee IN
AD  - Department of Medical Research, Chang Gung Memorial Hospital, Chiayi 61363, 
      Taiwan, R.O.C.
FAU - Huang, Cheng
AU  - Huang C
AD  - Department of Biotechnology and Laboratory Science in Medicine, National 
      Yang‑Ming University, Taipei 112, Taiwan, R.O.C.
FAU - Ku, Yu-Ju
AU  - Ku YJ
AD  - The Center for General Education of China Medical University, China Medical 
      University, Taichung 404, Taiwan, R.O.C.
FAU - Chen, Jui-Chieh
AU  - Chen JC
AD  - Department of Biochemical Science and Technology, National Chiayi University, 
      Chiayi 60004, Taiwan, R.O.C.
LA  - eng
PT  - Journal Article
DEP - 20190830
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Culture Media, Conditioned)
RN  - 5J49Q6B70F (Vincristine)
RN  - EC 2.7.11.1 (GSK3B protein, human)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
SB  - IM
MH  - Amphiregulin/genetics/*metabolism
MH  - Antineoplastic Agents/pharmacology
MH  - Carcinoma, Squamous Cell/drug therapy/genetics/*metabolism
MH  - Cell Line, Tumor
MH  - Culture Media, Conditioned/pharmacology
MH  - *Drug Resistance, Neoplasm
MH  - Gene Expression Regulation, Neoplastic
MH  - Gene Knockdown Techniques
MH  - Glycogen Synthase Kinase 3 beta/metabolism
MH  - Humans
MH  - Mouth Neoplasms/drug therapy/genetics/*metabolism
MH  - Prognosis
MH  - Signal Transduction
MH  - Up-Regulation
MH  - Vincristine/pharmacology
EDAT- 2019/09/06 06:00
MHDA- 2020/02/06 06:00
CRDT- 2019/09/06 06:00
PHST- 2019/02/27 00:00 [received]
PHST- 2019/08/01 00:00 [accepted]
PHST- 2019/09/06 06:00 [pubmed]
PHST- 2020/02/06 06:00 [medline]
PHST- 2019/09/06 06:00 [entrez]
AID - 10.3892/ijo.2019.4866 [doi]
PST - ppublish
SO  - Int J Oncol. 2019 Oct;55(4):949-959. doi: 10.3892/ijo.2019.4866. Epub 2019 Aug 
      30.