Antagonistic analogs of growth hormone-releasing hormone increase the efficacy of treatment of triple negative breast cancer in nude mice with doxorubicin; A preclinical study

Roberto Perez, Andrew V Schally, Petra Popovics, Renzhi Cai, Wei Sha, Ricardo Rincon, Ferenc G. Rick

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Introduction: This study evaluated the effects of an antagonistic analog of growth hormone-releasing hormone, MIA-602, on tumor growth, response to doxorubicin, expression of drug resistance genes, and efflux pump function in human triple negative breast cancers. Methods: HCC1806 (doxorubicin-sensitive) and MX-1 (doxorubicin-resistant), cell lines were xenografted into nude mice and treated with MIA-602, doxorubicin, or their combination. Tumors were evaluated for changes in volume and the expression of the drug resistance genes MDR1 and NANOG. In-vitro cell culture assays were used to analyze the effect of MIA-602 on efflux pump function. Results: Therapy with MIA-602 significantly reduced tumor growth and enhanced the efficacy of doxorubicin in both cell lines. Control HCC1806 tumors grew by 435%, while the volume of tumors treated with MIA-602 enlarged by 172.2% and with doxorubicin by 201.6%. Treatment with the combination of MIA-602 and doxorubicin resulted in an increase in volume of only 76.2%. Control MX-1 tumors grew by 907%, while tumors treated with MIA-602 enlarged by 434.8% and with doxorubicin by 815%. The combination of MIA-602 and doxorubicin reduced the increase in tumor volume to 256%. Treatment with MIA-602 lowered the level of growth hormonereleasing hormone and growth hormone-releasing hormone receptors and significantly reduced the expression of multidrug resistance (MDR1) gene and the drug resistance regulator NANOG. MIA-602 also suppressed efflux pump function in both cell lines. Conclusions: We conclude that treatment of triple negative breast cancers with growth hormone-releasing hormone antagonists reduces tumor growth and potentiates the effects of cytotoxic therapy by nullifying drug resistance.

Original languageEnglish (US)
Pages (from-to)665-673
Number of pages9
JournalOncoscience
Volume1
Issue number10
DOIs
StatePublished - 2014

Fingerprint

Triple Negative Breast Neoplasms
Growth Hormone-Releasing Hormone
Nude Mice
Doxorubicin
Drug Resistance
Neoplasms
Tumor Burden
Cell Line
Growth
GHRH(1-29)NH2, (PhAc-Ada)(0)-Tyr(1), Arg(2), Fpa(5,6), Ala(8), Har(9), Tyr(Me)(10), His(11), Orn(12,) Abu(15), His(20), Orn(21), Nle(27), Arg(28), Har(29)-
MDR Genes
Hormone Antagonists
Growth Hormone
Genes
Cell Culture Techniques

Keywords

  • Antagonist
  • Combination therapy
  • Drug resistance
  • GHRH analogs
  • Growth-hormone-releasing hormone
  • Triple negative breast cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Antagonistic analogs of growth hormone-releasing hormone increase the efficacy of treatment of triple negative breast cancer in nude mice with doxorubicin; A preclinical study. / Perez, Roberto; Schally, Andrew V; Popovics, Petra; Cai, Renzhi; Sha, Wei; Rincon, Ricardo; Rick, Ferenc G.

In: Oncoscience, Vol. 1, No. 10, 2014, p. 665-673.

Research output: Contribution to journalArticle

Perez, Roberto ; Schally, Andrew V ; Popovics, Petra ; Cai, Renzhi ; Sha, Wei ; Rincon, Ricardo ; Rick, Ferenc G. / Antagonistic analogs of growth hormone-releasing hormone increase the efficacy of treatment of triple negative breast cancer in nude mice with doxorubicin; A preclinical study. In: Oncoscience. 2014 ; Vol. 1, No. 10. pp. 665-673.
@article{36448d8276d24f05a4b0a5e8948b3d53,
title = "Antagonistic analogs of growth hormone-releasing hormone increase the efficacy of treatment of triple negative breast cancer in nude mice with doxorubicin; A preclinical study",
abstract = "Introduction: This study evaluated the effects of an antagonistic analog of growth hormone-releasing hormone, MIA-602, on tumor growth, response to doxorubicin, expression of drug resistance genes, and efflux pump function in human triple negative breast cancers. Methods: HCC1806 (doxorubicin-sensitive) and MX-1 (doxorubicin-resistant), cell lines were xenografted into nude mice and treated with MIA-602, doxorubicin, or their combination. Tumors were evaluated for changes in volume and the expression of the drug resistance genes MDR1 and NANOG. In-vitro cell culture assays were used to analyze the effect of MIA-602 on efflux pump function. Results: Therapy with MIA-602 significantly reduced tumor growth and enhanced the efficacy of doxorubicin in both cell lines. Control HCC1806 tumors grew by 435{\%}, while the volume of tumors treated with MIA-602 enlarged by 172.2{\%} and with doxorubicin by 201.6{\%}. Treatment with the combination of MIA-602 and doxorubicin resulted in an increase in volume of only 76.2{\%}. Control MX-1 tumors grew by 907{\%}, while tumors treated with MIA-602 enlarged by 434.8{\%} and with doxorubicin by 815{\%}. The combination of MIA-602 and doxorubicin reduced the increase in tumor volume to 256{\%}. Treatment with MIA-602 lowered the level of growth hormonereleasing hormone and growth hormone-releasing hormone receptors and significantly reduced the expression of multidrug resistance (MDR1) gene and the drug resistance regulator NANOG. MIA-602 also suppressed efflux pump function in both cell lines. Conclusions: We conclude that treatment of triple negative breast cancers with growth hormone-releasing hormone antagonists reduces tumor growth and potentiates the effects of cytotoxic therapy by nullifying drug resistance.",
keywords = "Antagonist, Combination therapy, Drug resistance, GHRH analogs, Growth-hormone-releasing hormone, Triple negative breast cancer",
author = "Roberto Perez and Schally, {Andrew V} and Petra Popovics and Renzhi Cai and Wei Sha and Ricardo Rincon and Rick, {Ferenc G.}",
year = "2014",
doi = "10.18632/oncoscience.92",
language = "English (US)",
volume = "1",
pages = "665--673",
journal = "Oncoscience",
issn = "2331-4737",
publisher = "Impact Journals",
number = "10",

}

TY - JOUR

T1 - Antagonistic analogs of growth hormone-releasing hormone increase the efficacy of treatment of triple negative breast cancer in nude mice with doxorubicin; A preclinical study

AU - Perez, Roberto

AU - Schally, Andrew V

AU - Popovics, Petra

AU - Cai, Renzhi

AU - Sha, Wei

AU - Rincon, Ricardo

AU - Rick, Ferenc G.

PY - 2014

Y1 - 2014

N2 - Introduction: This study evaluated the effects of an antagonistic analog of growth hormone-releasing hormone, MIA-602, on tumor growth, response to doxorubicin, expression of drug resistance genes, and efflux pump function in human triple negative breast cancers. Methods: HCC1806 (doxorubicin-sensitive) and MX-1 (doxorubicin-resistant), cell lines were xenografted into nude mice and treated with MIA-602, doxorubicin, or their combination. Tumors were evaluated for changes in volume and the expression of the drug resistance genes MDR1 and NANOG. In-vitro cell culture assays were used to analyze the effect of MIA-602 on efflux pump function. Results: Therapy with MIA-602 significantly reduced tumor growth and enhanced the efficacy of doxorubicin in both cell lines. Control HCC1806 tumors grew by 435%, while the volume of tumors treated with MIA-602 enlarged by 172.2% and with doxorubicin by 201.6%. Treatment with the combination of MIA-602 and doxorubicin resulted in an increase in volume of only 76.2%. Control MX-1 tumors grew by 907%, while tumors treated with MIA-602 enlarged by 434.8% and with doxorubicin by 815%. The combination of MIA-602 and doxorubicin reduced the increase in tumor volume to 256%. Treatment with MIA-602 lowered the level of growth hormonereleasing hormone and growth hormone-releasing hormone receptors and significantly reduced the expression of multidrug resistance (MDR1) gene and the drug resistance regulator NANOG. MIA-602 also suppressed efflux pump function in both cell lines. Conclusions: We conclude that treatment of triple negative breast cancers with growth hormone-releasing hormone antagonists reduces tumor growth and potentiates the effects of cytotoxic therapy by nullifying drug resistance.

AB - Introduction: This study evaluated the effects of an antagonistic analog of growth hormone-releasing hormone, MIA-602, on tumor growth, response to doxorubicin, expression of drug resistance genes, and efflux pump function in human triple negative breast cancers. Methods: HCC1806 (doxorubicin-sensitive) and MX-1 (doxorubicin-resistant), cell lines were xenografted into nude mice and treated with MIA-602, doxorubicin, or their combination. Tumors were evaluated for changes in volume and the expression of the drug resistance genes MDR1 and NANOG. In-vitro cell culture assays were used to analyze the effect of MIA-602 on efflux pump function. Results: Therapy with MIA-602 significantly reduced tumor growth and enhanced the efficacy of doxorubicin in both cell lines. Control HCC1806 tumors grew by 435%, while the volume of tumors treated with MIA-602 enlarged by 172.2% and with doxorubicin by 201.6%. Treatment with the combination of MIA-602 and doxorubicin resulted in an increase in volume of only 76.2%. Control MX-1 tumors grew by 907%, while tumors treated with MIA-602 enlarged by 434.8% and with doxorubicin by 815%. The combination of MIA-602 and doxorubicin reduced the increase in tumor volume to 256%. Treatment with MIA-602 lowered the level of growth hormonereleasing hormone and growth hormone-releasing hormone receptors and significantly reduced the expression of multidrug resistance (MDR1) gene and the drug resistance regulator NANOG. MIA-602 also suppressed efflux pump function in both cell lines. Conclusions: We conclude that treatment of triple negative breast cancers with growth hormone-releasing hormone antagonists reduces tumor growth and potentiates the effects of cytotoxic therapy by nullifying drug resistance.

KW - Antagonist

KW - Combination therapy

KW - Drug resistance

KW - GHRH analogs

KW - Growth-hormone-releasing hormone

KW - Triple negative breast cancer

UR - http://www.scopus.com/inward/record.url?scp=84924537778&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84924537778&partnerID=8YFLogxK

U2 - 10.18632/oncoscience.92

DO - 10.18632/oncoscience.92

M3 - Article

AN - SCOPUS:84924537778

VL - 1

SP - 665

EP - 673

JO - Oncoscience

JF - Oncoscience

SN - 2331-4737

IS - 10

ER -