摘要
| 原文 | 英語 |
|---|---|
| 頁（從 - 到） | 892-903 |
| 頁數 | 12 |
| 期刊 | Journal of Gene Medicine |
| 卷 | 12 |
| 發行號 | 11 |
| DOIs | |
| 出版狀態 | 已發佈 - 十一月 2010 |
| 對外發佈 | Yes |
指紋
ASJC Scopus subject areas
- Genetics
- Molecular Biology
- Molecular Medicine
- Genetics(clinical)
- Drug Discovery
引用此文
A novel targeting modality for renal cell carcinoma : Human osteocalcin promoter-mediated gene therapy synergistically induced by vitamin C and vitamin D3. / Johnson, Nicole A.; Chen, Bing Hung; Sung, Shian Ying; Liao, Chia Hui; Hsiao, Wan Chi; W.K. Chung, Leland; Hsieh, Chia Ling.
於: Journal of Gene Medicine, 卷 12, 編號 11, 11.2010, p. 892-903.研究成果: 雜誌貢獻 › 文章
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TY - JOUR
T1 - A novel targeting modality for renal cell carcinoma
T2 - Human osteocalcin promoter-mediated gene therapy synergistically induced by vitamin C and vitamin D3
AU - Johnson, Nicole A.
AU - Chen, Bing Hung
AU - Sung, Shian Ying
AU - Liao, Chia Hui
AU - Hsiao, Wan Chi
AU - W.K. Chung, Leland
AU - Hsieh, Chia Ling
PY - 2010/11
Y1 - 2010/11
N2 - Background: Advanced renal cell carcinoma (RCC) frequently develops skeletal metastasis and is highly resistant to conventional therapies. We hypothesized that the osteocalcin (OC) promoter may be a promising gene delivery system for RCC targeted gene therapy because osteotropic tumors gain osteomimetic properties and thrive in the new environment by exhibiting a bone-like gene expression profile. Human OC (hOC) expression is highly regulated by vitamins and hormone. In the present study, we tested the feasibility of vitamin-regulatable hOC promoter for RCC-specific transcriptional targeting, and examined the anti-tumor effect of vitamins C and D3 with hOC-based adenoviral vectors towards RCC. Methods: Real-time reverse transcriptase-polymerase chain reaction measured OC expression induced by vitamins C and D3, either alone or in combination, in RCC and normal human renal epithelial cells (HRE). The RCC-cytotoxic effects of concomitant vitamins and hOC promoter-based adenoviral vectors, Ad-hOC-TK and Ad-hOC-E1, were evaluated in both cell culture and a xenograft murine model. Results: We found that high doses of vitamin C induced H2O2-dependent apoptosis in RCC but not HRE. Treatment of RCC cells with combined vitamins C and D3 treatment significantly increased OC promoter activity compared to single reagent treatment. Combined vitamin therapy reduced tumor size (85%) and complete tumor regression occurred in 38% of mice co-administrated Ad-hOC-E1. Conclusions: The results obtained in the present study demonstrate that vitamins C and D3 synergized with the anti-tumor effects of therapeutic genes driven by hOC promoter through direct cytotoxicity as well as transcriptional targeting. This combined gene therapy provides a promising modality for advanced RCC targeted therapy.
AB - Background: Advanced renal cell carcinoma (RCC) frequently develops skeletal metastasis and is highly resistant to conventional therapies. We hypothesized that the osteocalcin (OC) promoter may be a promising gene delivery system for RCC targeted gene therapy because osteotropic tumors gain osteomimetic properties and thrive in the new environment by exhibiting a bone-like gene expression profile. Human OC (hOC) expression is highly regulated by vitamins and hormone. In the present study, we tested the feasibility of vitamin-regulatable hOC promoter for RCC-specific transcriptional targeting, and examined the anti-tumor effect of vitamins C and D3 with hOC-based adenoviral vectors towards RCC. Methods: Real-time reverse transcriptase-polymerase chain reaction measured OC expression induced by vitamins C and D3, either alone or in combination, in RCC and normal human renal epithelial cells (HRE). The RCC-cytotoxic effects of concomitant vitamins and hOC promoter-based adenoviral vectors, Ad-hOC-TK and Ad-hOC-E1, were evaluated in both cell culture and a xenograft murine model. Results: We found that high doses of vitamin C induced H2O2-dependent apoptosis in RCC but not HRE. Treatment of RCC cells with combined vitamins C and D3 treatment significantly increased OC promoter activity compared to single reagent treatment. Combined vitamin therapy reduced tumor size (85%) and complete tumor regression occurred in 38% of mice co-administrated Ad-hOC-E1. Conclusions: The results obtained in the present study demonstrate that vitamins C and D3 synergized with the anti-tumor effects of therapeutic genes driven by hOC promoter through direct cytotoxicity as well as transcriptional targeting. This combined gene therapy provides a promising modality for advanced RCC targeted therapy.
KW - Adenoviral vectors
KW - Gene therapy
KW - Osteocalcin promoter
KW - Renal cell carcinoma
KW - Vitamin C
KW - Vitamin D
UR - http://www.scopus.com/inward/record.url?scp=78649527524&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78649527524&partnerID=8YFLogxK
U2 - 10.1002/jgm.1516
DO - 10.1002/jgm.1516
M3 - Article
C2 - 21105150
AN - SCOPUS:78649527524
VL - 12
SP - 892
EP - 903
JO - Journal of Gene Medicine
JF - Journal of Gene Medicine
SN - 1099-498X
IS - 11
ER -