PMID- 28293855
OWN - NLM
STAT- MEDLINE
DCOM- 20180223
LR  - 20230722
IS  - 1868-8500 (Electronic)
IS  - 1868-8497 (Print)
IS  - 1868-8497 (Linking)
VI  - 8
IP  - 3
DP  - 2017 Jun
TI  - Growth Hormone Receptor Knockdown Sensitizes Human Melanoma Cells to Chemotherapy 
      by Attenuating Expression of ABC Drug Efflux Pumps.
PG  - 143-156
LID - 10.1007/s12672-017-0292-7 [doi]
AB  - Melanoma remains one of the most therapy-resistant forms of human cancer despite 
      recent introductions of highly efficacious targeted therapies. The intrinsic 
      therapy resistance of human melanoma is largely due to abundant expression of a 
      repertoire of xenobiotic efflux pumps of the ATP-binding cassette (ABC) 
      transporter family. Here, we report that GH action is a key mediator of 
      chemotherapeutic resistance in human melanoma cells. We investigated multiple ABC 
      efflux pumps (ABCB1, ABCB5, ABCB8, ABCC1, ABCC2, ABCG1, and ABCG2) reportedly 
      associated with melanoma drug resistance in different human melanoma cells and 
      tested the efficacy of five different anti-cancer compounds (cisplatin, 
      doxorubicin, oridonin, paclitaxel, vemurafenib) with decreased GH action. We 
      found that GH treatment of human melanoma cells upregulates expression of 
      multiple ABC transporters and increases the EC50 of melanoma drug vemurafenib. 
      Also, vemurafenib-resistant melanoma cells had upregulated levels of GH receptor 
      (GHR) expression as well as ABC efflux pumps. GHR knockdown (KD) using siRNA in 
      human melanoma cells treated with sub-EC50 doses of anti-tumor compounds resulted 
      in significantly increased drug retention, decreased cell proliferation and 
      increased drug efficacy, compared to mock-transfected controls. Our set of 
      findings identify an unknown mechanism of GH regulation in mediating melanoma 
      drug resistance and validates GHR as a unique therapeutic target for sensitizing 
      highly therapy-resistant human melanoma cells to lower doses of anti-cancer 
      drugs.
FAU - Basu, Reetobrata
AU  - Basu R
AUID- ORCID: 0000-0001-8415-1356
AD  - Edison Biotechnology Institute, Konneker Research Laboratory 206, Ohio 
      University, Athens, OH, 45701, USA.
AD  - Molecular and Cell Biology Program, Ohio University, Athens, OH, USA.
FAU - Baumgaertel, Nicholas
AU  - Baumgaertel N
AD  - Edison Biotechnology Institute, Konneker Research Laboratory 206, Ohio 
      University, Athens, OH, 45701, USA.
AD  - Department of Biological Sciences, Ohio University, Athens, OH, USA.
FAU - Wu, Shiyong
AU  - Wu S
AD  - Edison Biotechnology Institute, Konneker Research Laboratory 206, Ohio 
      University, Athens, OH, 45701, USA.
AD  - Molecular and Cell Biology Program, Ohio University, Athens, OH, USA.
FAU - Kopchick, John J
AU  - Kopchick JJ
AD  - Edison Biotechnology Institute, Konneker Research Laboratory 206, Ohio 
      University, Athens, OH, 45701, USA. kopchick@ohio.edu.
AD  - Molecular and Cell Biology Program, Ohio University, Athens, OH, USA. 
      kopchick@ohio.edu.
AD  - Heritage College of Osteopathic Medicine, Athens, OH, USA. kopchick@ohio.edu.
LA  - eng
PT  - Journal Article
DEP - 20170314
PL  - United States
TA  - Horm Cancer
JT  - Hormones & cancer
JID - 101518427
RN  - 0 (ABCC2 protein, human)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Indoles)
RN  - 0 (Multidrug Resistance-Associated Protein 2)
RN  - 0 (Receptors, Somatotropin)
RN  - 0 (Sulfonamides)
RN  - 207SMY3FQT (Vemurafenib)
RN  - 80168379AG (Doxorubicin)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Antineoplastic Agents/*administration & dosage
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Doxorubicin/administration & dosage
MH  - Drug Resistance, Neoplasm/*genetics
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Indoles/administration & dosage
MH  - Melanoma/*drug therapy/genetics/pathology
MH  - Multidrug Resistance-Associated Protein 2
MH  - Paclitaxel/administration & dosage
MH  - Receptors, Somatotropin/antagonists & inhibitors/*genetics
MH  - Sulfonamides/administration & dosage
MH  - Vemurafenib
PMC - PMC10355985
COIS- The authors declare that they have no conflict of interest.
EDAT- 2017/03/16 06:00
MHDA- 2018/02/24 06:00
PMCR- 2017/03/14
CRDT- 2017/03/16 06:00
PHST- 2016/12/11 00:00 [received]
PHST- 2017/03/02 00:00 [accepted]
PHST- 2017/03/16 06:00 [pubmed]
PHST- 2018/02/24 06:00 [medline]
PHST- 2017/03/16 06:00 [entrez]
PHST- 2017/03/14 00:00 [pmc-release]
AID - 10.1007/s12672-017-0292-7 [pii]
AID - 292 [pii]
AID - 10.1007/s12672-017-0292-7 [doi]
PST - ppublish
SO  - Horm Cancer. 2017 Jun;8(3):143-156. doi: 10.1007/s12672-017-0292-7. Epub 2017 Mar 
      14.