Suppression of ErbB-2 in androgen-independent human prostate cancer cells enhances cytotoxic effect by gemcitabine in an androgen-reduced environment

Li Zhang; Jeffrey S. Davis; Stanislav Zelivianski; Fen Fen Lin; Rachel Schutte; Thomas L. Davis; Ralph Hauke; Surinder K. Batra; Ming Fong Lin

doi:10.1016/j.canlet.2009.04.041

Suppression of ErbB-2 in androgen-independent human prostate cancer cells enhances cytotoxic effect by gemcitabine in an androgen-reduced environment

Li Zhang, Jeffrey S. Davis, Stanislav Zelivianski, Fen Fen Lin, Rachel Schutte, Thomas L. Davis, Ralph Hauke, Surinder K. Batra, Ming Fong Lin

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

We examined the efficacy of combination treatments utilizing cytotoxic drugs plus inhibitors to members of the ErbB-ERK signal pathway in human prostate cancer (PCa) LNCaP C-81 cells. Under an androgen-reduced condition, 50 nM gemcitabine caused about 40% growth suppression on C-81 cells. Simultaneous treatment of gemcitabine plus 10 μM AG825 produced 60% suppression (p < 0.03); while, 85% growth inhibition (p < 0.02) was seen if AG825 was added to gemcitabine-treated cells after a 24 h-interval. Our data thus showed that in androgen-reduced conditions, inhibition of ErbB-2 increases the cytotoxic efficacy of gemcitabine in PCa cells. This finding has significant implications in the choice of drugs for combination therapy as well as the order of administration for treating cancer patients.

Original language	English (US)
Pages (from-to)	58-65
Number of pages	8
Journal	Cancer Letters
Volume	285
Issue number	1
DOIs	https://doi.org/10.1016/j.canlet.2009.04.041
State	Published - Nov 18 2009

Keywords

Combination therapy
ErbB-2 inhibitor
Gemcitabine
Hormone-refractory prostate cancer

ASJC Scopus subject areas

Oncology
Cancer Research

Access to Document

10.1016/j.canlet.2009.04.041

Cite this

@article{bbe2c0bb064543ea8fc3de4b8162de35,

title = "Suppression of ErbB-2 in androgen-independent human prostate cancer cells enhances cytotoxic effect by gemcitabine in an androgen-reduced environment",

abstract = "We examined the efficacy of combination treatments utilizing cytotoxic drugs plus inhibitors to members of the ErbB-ERK signal pathway in human prostate cancer (PCa) LNCaP C-81 cells. Under an androgen-reduced condition, 50 nM gemcitabine caused about 40% growth suppression on C-81 cells. Simultaneous treatment of gemcitabine plus 10 μM AG825 produced 60% suppression (p < 0.03); while, 85% growth inhibition (p < 0.02) was seen if AG825 was added to gemcitabine-treated cells after a 24 h-interval. Our data thus showed that in androgen-reduced conditions, inhibition of ErbB-2 increases the cytotoxic efficacy of gemcitabine in PCa cells. This finding has significant implications in the choice of drugs for combination therapy as well as the order of administration for treating cancer patients.",

keywords = "Combination therapy, ErbB-2 inhibitor, Gemcitabine, Hormone-refractory prostate cancer",

author = "Li Zhang and Davis, {Jeffrey S.} and Stanislav Zelivianski and Lin, {Fen Fen} and Rachel Schutte and Davis, {Thomas L.} and Ralph Hauke and Batra, {Surinder K.} and Lin, {Ming Fong}",

note = "Funding Information: This study is supported in part by NIH Grant (2R01 CA88184) and DOD (PC074289 and PC050769). We thank Drs. Mark Kellerman and Matthew Spellman for participating in the early phase of studies and Dr. Suresh Veeramani for his valuable discussion and comments.",

year = "2009",

month = nov,

day = "18",

doi = "10.1016/j.canlet.2009.04.041",

language = "English (US)",

volume = "285",

pages = "58--65",

journal = "Cancer Letters",

issn = "0304-3835",

publisher = "Elsevier Ireland Ltd",

number = "1",

}

TY - JOUR

T1 - Suppression of ErbB-2 in androgen-independent human prostate cancer cells enhances cytotoxic effect by gemcitabine in an androgen-reduced environment

AU - Zhang, Li

AU - Davis, Jeffrey S.

AU - Zelivianski, Stanislav

AU - Lin, Fen Fen

AU - Schutte, Rachel

AU - Davis, Thomas L.

AU - Hauke, Ralph

AU - Batra, Surinder K.

AU - Lin, Ming Fong

N1 - Funding Information: This study is supported in part by NIH Grant (2R01 CA88184) and DOD (PC074289 and PC050769). We thank Drs. Mark Kellerman and Matthew Spellman for participating in the early phase of studies and Dr. Suresh Veeramani for his valuable discussion and comments.

PY - 2009/11/18

Y1 - 2009/11/18

N2 - We examined the efficacy of combination treatments utilizing cytotoxic drugs plus inhibitors to members of the ErbB-ERK signal pathway in human prostate cancer (PCa) LNCaP C-81 cells. Under an androgen-reduced condition, 50 nM gemcitabine caused about 40% growth suppression on C-81 cells. Simultaneous treatment of gemcitabine plus 10 μM AG825 produced 60% suppression (p < 0.03); while, 85% growth inhibition (p < 0.02) was seen if AG825 was added to gemcitabine-treated cells after a 24 h-interval. Our data thus showed that in androgen-reduced conditions, inhibition of ErbB-2 increases the cytotoxic efficacy of gemcitabine in PCa cells. This finding has significant implications in the choice of drugs for combination therapy as well as the order of administration for treating cancer patients.

AB - We examined the efficacy of combination treatments utilizing cytotoxic drugs plus inhibitors to members of the ErbB-ERK signal pathway in human prostate cancer (PCa) LNCaP C-81 cells. Under an androgen-reduced condition, 50 nM gemcitabine caused about 40% growth suppression on C-81 cells. Simultaneous treatment of gemcitabine plus 10 μM AG825 produced 60% suppression (p < 0.03); while, 85% growth inhibition (p < 0.02) was seen if AG825 was added to gemcitabine-treated cells after a 24 h-interval. Our data thus showed that in androgen-reduced conditions, inhibition of ErbB-2 increases the cytotoxic efficacy of gemcitabine in PCa cells. This finding has significant implications in the choice of drugs for combination therapy as well as the order of administration for treating cancer patients.

KW - Combination therapy

KW - ErbB-2 inhibitor

KW - Gemcitabine

KW - Hormone-refractory prostate cancer

UR - http://www.scopus.com/inward/record.url?scp=70349270611&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70349270611&partnerID=8YFLogxK

U2 - 10.1016/j.canlet.2009.04.041

DO - 10.1016/j.canlet.2009.04.041

M3 - Article

C2 - 19467571

AN - SCOPUS:70349270611

SN - 0304-3835

VL - 285

SP - 58

EP - 65

JO - Cancer Letters

JF - Cancer Letters

IS - 1

ER -

Suppression of ErbB-2 in androgen-independent human prostate cancer cells enhances cytotoxic effect by gemcitabine in an androgen-reduced environment

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this