Significance of combination therapy of zoledronic acid and gemcitabine on pancreatic cancer

Ming Zhao, Yohei Tominaga, Kenoki Ohuchida, Kazuhiro Mizumoto, Lin Cui, Shingo Kozono, Hayato Fujita, Ryo Maeyama, Hiroki Toma, Masao Tanaka

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

In the present study, we examined the cytotoxic effects of combination therapy with zoledronic acid (ZOL) and gemcitabine (GEM) on pancreatic cancer cells in vitro and in vivo. Four human pancreatic cancer cell lines were treated with ZOL, GEM or a combination of both, and the effects of the respective drug regimens on cell proliferation, invasion and matrix metalloproteinase (MMP) expression were examined. A pancreatic cancer cell line was also intrasplenically or orthotopically implanted into athymic mice and the effects of these drugs on tumor metastasis and growth in vivo were evaluated by histological and immunohistochemical analyses. Combination treatment with low doses of ZOL and GEM efficiently inhibited the proliferation (P<0.001) and invasion (P<0.001) of pancreatic cancer cells in vitro. Western blotting assay revealed that MMP-2 and MMP-9 expression levels were decreased after ZOL treatment. In vivo, combined treatment significantly inhibited tumor growth (P<0.05) and the development of liver metastasis (P<0.05). These data revealed that ZOL and GEM, when used in combination, have significant antitumor, anti-metastatic and anti-angiogenic effects on pancreatic cancer cells. The present study is the first to report the significance of the combination treatment of ZOL and GEM in pancreatic cancer using an in vivo model. These data are promising for the future application of this drug regimen in patients with pancreatic cancer.

Original languageEnglish
Pages (from-to)58-66
Number of pages9
JournalCancer Science
Volume103
Issue number1
DOIs
Publication statusPublished - Jan 1 2012

Fingerprint

zoledronic acid
gemcitabine
Pancreatic Neoplasms
Therapeutics
Pharmaceutical Preparations
Neoplasm Metastasis
Cell Line
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Growth
Matrix Metalloproteinases
Nude Mice
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Significance of combination therapy of zoledronic acid and gemcitabine on pancreatic cancer. / Zhao, Ming; Tominaga, Yohei; Ohuchida, Kenoki; Mizumoto, Kazuhiro; Cui, Lin; Kozono, Shingo; Fujita, Hayato; Maeyama, Ryo; Toma, Hiroki; Tanaka, Masao.

In: Cancer Science, Vol. 103, No. 1, 01.01.2012, p. 58-66.

Research output: Contribution to journalArticle

Zhao, Ming ; Tominaga, Yohei ; Ohuchida, Kenoki ; Mizumoto, Kazuhiro ; Cui, Lin ; Kozono, Shingo ; Fujita, Hayato ; Maeyama, Ryo ; Toma, Hiroki ; Tanaka, Masao. / Significance of combination therapy of zoledronic acid and gemcitabine on pancreatic cancer. In: Cancer Science. 2012 ; Vol. 103, No. 1. pp. 58-66.
@article{1d91c47ea9f44a328c1de90c571cfdb1,
title = "Significance of combination therapy of zoledronic acid and gemcitabine on pancreatic cancer",
abstract = "In the present study, we examined the cytotoxic effects of combination therapy with zoledronic acid (ZOL) and gemcitabine (GEM) on pancreatic cancer cells in vitro and in vivo. Four human pancreatic cancer cell lines were treated with ZOL, GEM or a combination of both, and the effects of the respective drug regimens on cell proliferation, invasion and matrix metalloproteinase (MMP) expression were examined. A pancreatic cancer cell line was also intrasplenically or orthotopically implanted into athymic mice and the effects of these drugs on tumor metastasis and growth in vivo were evaluated by histological and immunohistochemical analyses. Combination treatment with low doses of ZOL and GEM efficiently inhibited the proliferation (P<0.001) and invasion (P<0.001) of pancreatic cancer cells in vitro. Western blotting assay revealed that MMP-2 and MMP-9 expression levels were decreased after ZOL treatment. In vivo, combined treatment significantly inhibited tumor growth (P<0.05) and the development of liver metastasis (P<0.05). These data revealed that ZOL and GEM, when used in combination, have significant antitumor, anti-metastatic and anti-angiogenic effects on pancreatic cancer cells. The present study is the first to report the significance of the combination treatment of ZOL and GEM in pancreatic cancer using an in vivo model. These data are promising for the future application of this drug regimen in patients with pancreatic cancer.",
author = "Ming Zhao and Yohei Tominaga and Kenoki Ohuchida and Kazuhiro Mizumoto and Lin Cui and Shingo Kozono and Hayato Fujita and Ryo Maeyama and Hiroki Toma and Masao Tanaka",
year = "2012",
month = "1",
day = "1",
doi = "10.1111/j.1349-7006.2011.02113.x",
language = "English",
volume = "103",
pages = "58--66",
journal = "Cancer Science",
issn = "1347-9032",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Significance of combination therapy of zoledronic acid and gemcitabine on pancreatic cancer

AU - Zhao, Ming

AU - Tominaga, Yohei

AU - Ohuchida, Kenoki

AU - Mizumoto, Kazuhiro

AU - Cui, Lin

AU - Kozono, Shingo

AU - Fujita, Hayato

AU - Maeyama, Ryo

AU - Toma, Hiroki

AU - Tanaka, Masao

PY - 2012/1/1

Y1 - 2012/1/1

N2 - In the present study, we examined the cytotoxic effects of combination therapy with zoledronic acid (ZOL) and gemcitabine (GEM) on pancreatic cancer cells in vitro and in vivo. Four human pancreatic cancer cell lines were treated with ZOL, GEM or a combination of both, and the effects of the respective drug regimens on cell proliferation, invasion and matrix metalloproteinase (MMP) expression were examined. A pancreatic cancer cell line was also intrasplenically or orthotopically implanted into athymic mice and the effects of these drugs on tumor metastasis and growth in vivo were evaluated by histological and immunohistochemical analyses. Combination treatment with low doses of ZOL and GEM efficiently inhibited the proliferation (P<0.001) and invasion (P<0.001) of pancreatic cancer cells in vitro. Western blotting assay revealed that MMP-2 and MMP-9 expression levels were decreased after ZOL treatment. In vivo, combined treatment significantly inhibited tumor growth (P<0.05) and the development of liver metastasis (P<0.05). These data revealed that ZOL and GEM, when used in combination, have significant antitumor, anti-metastatic and anti-angiogenic effects on pancreatic cancer cells. The present study is the first to report the significance of the combination treatment of ZOL and GEM in pancreatic cancer using an in vivo model. These data are promising for the future application of this drug regimen in patients with pancreatic cancer.

AB - In the present study, we examined the cytotoxic effects of combination therapy with zoledronic acid (ZOL) and gemcitabine (GEM) on pancreatic cancer cells in vitro and in vivo. Four human pancreatic cancer cell lines were treated with ZOL, GEM or a combination of both, and the effects of the respective drug regimens on cell proliferation, invasion and matrix metalloproteinase (MMP) expression were examined. A pancreatic cancer cell line was also intrasplenically or orthotopically implanted into athymic mice and the effects of these drugs on tumor metastasis and growth in vivo were evaluated by histological and immunohistochemical analyses. Combination treatment with low doses of ZOL and GEM efficiently inhibited the proliferation (P<0.001) and invasion (P<0.001) of pancreatic cancer cells in vitro. Western blotting assay revealed that MMP-2 and MMP-9 expression levels were decreased after ZOL treatment. In vivo, combined treatment significantly inhibited tumor growth (P<0.05) and the development of liver metastasis (P<0.05). These data revealed that ZOL and GEM, when used in combination, have significant antitumor, anti-metastatic and anti-angiogenic effects on pancreatic cancer cells. The present study is the first to report the significance of the combination treatment of ZOL and GEM in pancreatic cancer using an in vivo model. These data are promising for the future application of this drug regimen in patients with pancreatic cancer.

UR - http://www.scopus.com/inward/record.url?scp=84855488454&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84855488454&partnerID=8YFLogxK

U2 - 10.1111/j.1349-7006.2011.02113.x

DO - 10.1111/j.1349-7006.2011.02113.x

M3 - Article

C2 - 21954965

AN - SCOPUS:84855488454

VL - 103

SP - 58

EP - 66

JO - Cancer Science

JF - Cancer Science

SN - 1347-9032

IS - 1

ER -