Cationic liposome-mediated transfection of CD40 ligand gene inhibits hepatic tumor growth of hepatocellular carcinoma in mice / 浙江大学学报(英文版)(B辑:生物医学和生物技术)
Journal of Zhejiang University. Science. B
; (12): 7-13, 2009.
Article
en En
| WPRIM
| ID: wpr-335407
Biblioteca responsable:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the efficacy of cationic liposome-mediated CD40 ligand (CD40L) gene therapy for hepatocellular carcinoma.</p><p><b>METHODS</b>1x10(6) of parental H22 cells or H22 cells transfected with the expression vector containing murine CD40L cDNA encoding the entire coding region (pcDNA3.1(+)-mCD40L) were inoculated subcutaneously into the left flanks of syngenic BALB/C mice. The tumor-bearing mice (tumor nodules 10 mm in maximal diameter) received the treatment of the intratumoral injection of pcDNA3.1(+)-mCD40L/Transfectam, pcDNA3.1(+), or phosphate-buffered saline (PBS), or no treatment. The mice were monitored for tumor growth weekly. We examined mCD40L messenger ribonucleic acid (mRNA) expression by reverse transcription polymerase chain reaction (RT-PCR) and the histologic changes in tumors at two weeks after intratumoral injection using immunohistochemical staining of tumor tissues.</p><p><b>RESULTS</b>All mice inoculated with parental H22 cells developed a tumor subcutaneously, and the tumor size increased progressively within three weeks. However, the mice receiving H22-CD40L cells exhibited complete regression of the tumor two weeks after tumor cell inoculation. The tumor-bearing animals with the treatment of pcDNA3.1(+) or PBS, or without treatment had progressive tumor growth, while those mice treated with pcDNA3.1(+)-mCD40L exhibited a significant inhibition of tumor growth. RT-PCR analysis showed that 783-bp fragments corresponding to the mCD40L mRNA were amplified only from pcDNA3.1(+)-mCD40L treated tumors. The tumor samples from pcDNA3.1(+)-mCD40L-treated mice showed significant lymphocyte infiltration, apoptotic bodies, and confluent necrosis in the tumor tissues.</p><p><b>CONCLUSION</b>The tumorigenicity of CD40L-expressing cells was abrogated when the cells were implanted subcutaneously. In vivo gene therapy of established liver tumor nodules in mice by the intratumoral injection of pcDNA3.1(+)-mCD40L led to significant tumor inhibition. There was mCD40L mRNA expression in the tissues from pcDNA3.1(+)-mCD40L-treated tumors. The intratumoral injection of pcDNA3.1(+)-mCD40L induced a strong inflammatory, mainly lymphocytic infiltration of the tumor, and increased the necrotic rate of the neoplastic cells.</p>
Texto completo:
1
Índice:
WPRIM
Asunto principal:
Patología
/
Terapéutica
/
Transfección
/
Terapia Genética
/
Cationes
/
Química
/
Resultado del Tratamiento
/
Carcinoma Hepatocelular
/
Ligando de CD40
/
Usos Terapéuticos
Límite:
Animals
Idioma:
En
Revista:
Journal of Zhejiang University. Science. B
Año:
2009
Tipo del documento:
Article