Hormones and Cancer

, Volume 8, Issue 3, pp 143–156 | Cite as

Growth Hormone Receptor Knockdown Sensitizes Human Melanoma Cells to Chemotherapy by Attenuating Expression of ABC Drug Efflux Pumps

  • Reetobrata Basu
  • Nicholas Baumgaertel
  • Shiyong Wu
  • John J. KopchickEmail author
Original Paper


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.


Melanoma Paclitaxel Melanoma Cell Efflux Pump Melanoma Cell Line 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


This work was supported in part by the State of Ohio’s Eminent Scholar Program that includes a gift from Milton and Lawrence Goll, by the AMVETS, and the Edison Biotechnology Institute at Ohio University.

Supplementary material

12672_2017_292_MOESM1_ESM.pptx (3.7 mb)
ESM 1 (PPTX 3776 kb)


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Edison Biotechnology Institute, Konneker Research Laboratory 206Ohio UniversityAthensUSA
  2. 2.Molecular and Cell Biology ProgramOhio UniversityAthensUSA
  3. 3.Department of Biological SciencesOhio UniversityAthensUSA
  4. 4.Heritage College of Osteopathic MedicineAthensUSA

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