Synergic effects of the combination of VEGF-targeted shRNA and taxol on human prostate cancer DU145 both in vitro and in vivo.
- Author:
Bao-wei LI
1
;
Min ZHANG
;
Hong-wei HE
;
Sheng-hua ZHANG
;
Rong-guang SHAO
Author Information
1. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Antineoplastic Agents, Phytogenic;
pharmacology;
Cell Line, Tumor;
Cell Movement;
drug effects;
Cell Proliferation;
drug effects;
Genetic Vectors;
Humans;
Male;
Mice;
Mice, Inbred BALB C;
Mice, Nude;
Neoplasm Transplantation;
Paclitaxel;
pharmacology;
Plasmids;
Prostatic Neoplasms;
metabolism;
pathology;
RNA Interference;
RNA, Small Interfering;
genetics;
Transfection;
Tubulin Modulators;
pharmacology;
Tumor Burden;
drug effects;
Vascular Endothelial Growth Factor A;
genetics;
metabolism;
Vincristine;
pharmacology
- From:
Acta Pharmaceutica Sinica
2009;44(3):296-302
- CountryChina
- Language:Chinese
-
Abstract:
In this study, the antitumor activities of VEGF shRNA and tubulin inhibitors on human prostate cancer DU145 cells was investigated, and shRNA transient expression plasmid pCSH1-VEGF targeting VEGF mRNA was constructed. The silence efficiency of pCSH1-VEGF was detected by RT-PCR assay, Western blotting, and Matrigel invasion assay. The sensitivity change of DU145 cells to Taxol and vincristine (VCR) was measured by MTT assay. To detect the effects of pCSH1-VEGF and Taxol in vivo, nude mice model of DU145 xenograft tumor was established by subcutaneous inoculation. The results showed that transcription and expression of VEGF were knocked by pCSH1-VEGF in DU145 cells. Matrigel invasion assay results showed that pCSH1-VEGF significantly reduced the migration of DU145 cells with inhibitory rate of 56.1%. Furthermore, pCSH1-VEGF enhanced the sensitivity of DU145 cells to Taxol and vincristine, and the values of IC50 decreased by 77.3% and 92.6%, respectively. In vivo experiment showed that Taxol, pCSH1-VEGF, combination of pCSH1-VEGF and Taxol inhibited tumor growth by the rates of 48.8%, 56.2% and 81.8%, respectively. The coefficient of drug interaction (CDI) of pCSH1-VEGF and Taxol was 0.82. The data suggested that VEGF shRNA could significantly enhance the sensitivity of human prostate cancer to tubulin inhibitors.
