Skin delivery of short hairpin RNA of indoleamine 2,3 dioxygenase induces antitumor immunity against orthotopic and metastatic liver cancer

Tzu Ting Huang, Meng Chi Yen, Chi Chen Lin, Tzu Yang Weng, Yi Ling Chen, Chiu Mei Lin, Ming-Derg Lai

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Liver cancer is one of the most malignant cancers in the world and has a high rate of metastasis. Therefore, development of a novel therapy for liver cancer is a critical issue. Indoleamine 2,3-dioxygenase (IDO) is known as a negative immune regulator in dendritic cells. Our previous study demonstrated that skin delivery of IDO short hairpin RNA (shRNA) induced antitumor immunity in subcutaneous bladder and colon tumor models. Because the immunological environment is quite different between skin and liver, it is essential to evaluate whether skin delivery of IDO shRNA is an effective treatment in metastatic and orthotopic animal tumor models. In the present study, IDO shRNA inhibited tumor growth in subcutaneous, metastatic and orthotopic liver tumor models. The cytotoxicity of splenocytes was significantly elevated in mice treated with IDO shRNA in the orthotopic and metastatic tumor models. Interleukin (IL)-12 and interferon (IFN)-gamma mRNA expression were upregulated while IL-10 was downregulated in the inguinal lymph nodes, which were collected from IDO shRNA-treated mice. Similar results were observed in the spleens of mice inoculated with IDO shRNA by gene gun. The results indicate that skin administration of IDO shRNA is an effective therapy in orthotopic and metastatic liver cancer animal models. Indoleamine 2,3-dioxygenase shRNA might be a potential new treatment for liver cancer in the future.

Original languageEnglish
Pages (from-to)2214-2220
Number of pages7
JournalCancer Science
Volume102
Issue number12
DOIs
Publication statusPublished - 2011 Dec 1

Fingerprint

Indoleamine-Pyrrole 2,3,-Dioxygenase
Liver Neoplasms
Small Interfering RNA
Immunity
Skin
Neoplasms
Animal Models
Groin
Liver
Firearms
Interleukin-12
Urinary Bladder Neoplasms
Interleukin-10
Dendritic Cells
Interferon-gamma
Colon
Down-Regulation
Spleen
Lymph Nodes
Neoplasm Metastasis

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Huang, Tzu Ting ; Yen, Meng Chi ; Lin, Chi Chen ; Weng, Tzu Yang ; Chen, Yi Ling ; Lin, Chiu Mei ; Lai, Ming-Derg. / Skin delivery of short hairpin RNA of indoleamine 2,3 dioxygenase induces antitumor immunity against orthotopic and metastatic liver cancer. In: Cancer Science. 2011 ; Vol. 102, No. 12. pp. 2214-2220.
@article{7b3f8671f9cb4cb8a702edbb8f225de4,
title = "Skin delivery of short hairpin RNA of indoleamine 2,3 dioxygenase induces antitumor immunity against orthotopic and metastatic liver cancer",
abstract = "Liver cancer is one of the most malignant cancers in the world and has a high rate of metastasis. Therefore, development of a novel therapy for liver cancer is a critical issue. Indoleamine 2,3-dioxygenase (IDO) is known as a negative immune regulator in dendritic cells. Our previous study demonstrated that skin delivery of IDO short hairpin RNA (shRNA) induced antitumor immunity in subcutaneous bladder and colon tumor models. Because the immunological environment is quite different between skin and liver, it is essential to evaluate whether skin delivery of IDO shRNA is an effective treatment in metastatic and orthotopic animal tumor models. In the present study, IDO shRNA inhibited tumor growth in subcutaneous, metastatic and orthotopic liver tumor models. The cytotoxicity of splenocytes was significantly elevated in mice treated with IDO shRNA in the orthotopic and metastatic tumor models. Interleukin (IL)-12 and interferon (IFN)-gamma mRNA expression were upregulated while IL-10 was downregulated in the inguinal lymph nodes, which were collected from IDO shRNA-treated mice. Similar results were observed in the spleens of mice inoculated with IDO shRNA by gene gun. The results indicate that skin administration of IDO shRNA is an effective therapy in orthotopic and metastatic liver cancer animal models. Indoleamine 2,3-dioxygenase shRNA might be a potential new treatment for liver cancer in the future.",
author = "Huang, {Tzu Ting} and Yen, {Meng Chi} and Lin, {Chi Chen} and Weng, {Tzu Yang} and Chen, {Yi Ling} and Lin, {Chiu Mei} and Ming-Derg Lai",
year = "2011",
month = "12",
day = "1",
doi = "10.1111/j.1349-7006.2011.02094.x",
language = "English",
volume = "102",
pages = "2214--2220",
journal = "Cancer Science",
issn = "1347-9032",
publisher = "Wiley-Blackwell",
number = "12",

}

Skin delivery of short hairpin RNA of indoleamine 2,3 dioxygenase induces antitumor immunity against orthotopic and metastatic liver cancer. / Huang, Tzu Ting; Yen, Meng Chi; Lin, Chi Chen; Weng, Tzu Yang; Chen, Yi Ling; Lin, Chiu Mei; Lai, Ming-Derg.

In: Cancer Science, Vol. 102, No. 12, 01.12.2011, p. 2214-2220.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Skin delivery of short hairpin RNA of indoleamine 2,3 dioxygenase induces antitumor immunity against orthotopic and metastatic liver cancer

AU - Huang, Tzu Ting

AU - Yen, Meng Chi

AU - Lin, Chi Chen

AU - Weng, Tzu Yang

AU - Chen, Yi Ling

AU - Lin, Chiu Mei

AU - Lai, Ming-Derg

PY - 2011/12/1

Y1 - 2011/12/1

N2 - Liver cancer is one of the most malignant cancers in the world and has a high rate of metastasis. Therefore, development of a novel therapy for liver cancer is a critical issue. Indoleamine 2,3-dioxygenase (IDO) is known as a negative immune regulator in dendritic cells. Our previous study demonstrated that skin delivery of IDO short hairpin RNA (shRNA) induced antitumor immunity in subcutaneous bladder and colon tumor models. Because the immunological environment is quite different between skin and liver, it is essential to evaluate whether skin delivery of IDO shRNA is an effective treatment in metastatic and orthotopic animal tumor models. In the present study, IDO shRNA inhibited tumor growth in subcutaneous, metastatic and orthotopic liver tumor models. The cytotoxicity of splenocytes was significantly elevated in mice treated with IDO shRNA in the orthotopic and metastatic tumor models. Interleukin (IL)-12 and interferon (IFN)-gamma mRNA expression were upregulated while IL-10 was downregulated in the inguinal lymph nodes, which were collected from IDO shRNA-treated mice. Similar results were observed in the spleens of mice inoculated with IDO shRNA by gene gun. The results indicate that skin administration of IDO shRNA is an effective therapy in orthotopic and metastatic liver cancer animal models. Indoleamine 2,3-dioxygenase shRNA might be a potential new treatment for liver cancer in the future.

AB - Liver cancer is one of the most malignant cancers in the world and has a high rate of metastasis. Therefore, development of a novel therapy for liver cancer is a critical issue. Indoleamine 2,3-dioxygenase (IDO) is known as a negative immune regulator in dendritic cells. Our previous study demonstrated that skin delivery of IDO short hairpin RNA (shRNA) induced antitumor immunity in subcutaneous bladder and colon tumor models. Because the immunological environment is quite different between skin and liver, it is essential to evaluate whether skin delivery of IDO shRNA is an effective treatment in metastatic and orthotopic animal tumor models. In the present study, IDO shRNA inhibited tumor growth in subcutaneous, metastatic and orthotopic liver tumor models. The cytotoxicity of splenocytes was significantly elevated in mice treated with IDO shRNA in the orthotopic and metastatic tumor models. Interleukin (IL)-12 and interferon (IFN)-gamma mRNA expression were upregulated while IL-10 was downregulated in the inguinal lymph nodes, which were collected from IDO shRNA-treated mice. Similar results were observed in the spleens of mice inoculated with IDO shRNA by gene gun. The results indicate that skin administration of IDO shRNA is an effective therapy in orthotopic and metastatic liver cancer animal models. Indoleamine 2,3-dioxygenase shRNA might be a potential new treatment for liver cancer in the future.

UR - http://www.scopus.com/inward/record.url?scp=81855161873&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=81855161873&partnerID=8YFLogxK

U2 - 10.1111/j.1349-7006.2011.02094.x

DO - 10.1111/j.1349-7006.2011.02094.x

M3 - Article

VL - 102

SP - 2214

EP - 2220

JO - Cancer Science

JF - Cancer Science

SN - 1347-9032

IS - 12

ER -