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Recombinant adenovirus IL-24-Bax promotes apoptosis of hepatocellular carcinoma cells in vitro and in vivo.

Li J, Shi L, Zhang X, Kang X, Wen Y, Qian H, Zhou Y, Xu W, Zhang Y, Wu M, Yin Z - Cancer Gene Ther. (2010)

Bottom Line: The mechanism of this response may include the effect of the 10HRE/VEGF385 promoter and the synergistic effect of IL-24 and Bax.Ad.IL-24-Bax also suppressed tumor growth in nude mice and induced apoptosis.Ad.IL-24-Bax may be a useful tool for gene therapy of hepatic cancer.

View Article: PubMed Central - PubMed

Affiliation: Molecular Oncology Laboratory, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.

ABSTRACT
Gene therapy promises to become an alternative choice for the treatment of hepatic cancer. In many cancers, the delivery of chimeric proteins by adenovirus vector has been reported to induce apoptosis. This study was performed to evaluate whether the recombinant adenovirus interleukin (IL)-24-Bax can induce apoptosis in hepatocellular carcinoma cells in vitro and in vivo. Several recombinant adenoviruses were constructed, and the expression of their encoded proteins was measured. The effects of the recombinant adenovirus on hepatocellular carcinoma cells and the normal hepatocyte cell line were investigated through cell viability and apoptosis assays after the cells were treated with Ad.Luc, Ad.IL-24, Ad.Bax or Ad.IL-24-Bax. The mechanism involved was also explored. A tumor-bearing mouse model was used to evaluate the effects of the adenovirus on tumor volume and cell apoptosis in vivo. Ad.IL-24-Bax selectively suppressed growth of hepatocellular carcinoma cells and induced apoptosis, but it had little influence on the normal hepatocytes. The mechanism of this response may include the effect of the 10HRE/VEGF385 promoter and the synergistic effect of IL-24 and Bax. Ad.IL-24-Bax also suppressed tumor growth in nude mice and induced apoptosis. Ad.IL-24-Bax may be a useful tool for gene therapy of hepatic cancer.

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Ad.IL-24-Bax suppressed the proliferation of hepatocellular carcinoma cells and induced apoptosis in hepatocellular carcinoma in vitro. (a) Cell viability after Ad.IL-24-Bax treatment by methyl thiazolyl tetrazolium assays. Normal hepatocyte (L02) and hepatocellular carcinoma cells (HepG2, Hep3B, PLC/PRF/5) were treated with Ad.Luc (◊), Ad.Bax (), Ad.IL-24 (▴) or Ad.IL-24-Bax (▪) at different multiplicities of infection (MOI). Three days after infection, the cell survival rate was checked. Ad.IL-24-Bax inhibited hepatocellular carcinoma cell growth, while having little influence on the growth of normal liver cells. (b) Percentage of apoptotic cells after Ad.IL-24-Bax treatment using the Annexin V-fluorescein isothiocyanate/proliferation index staining method. Normal hepatocytes (L02) and hepatocellular carcinoma cells (HepG2, Hep3B, PLC/PRF/5) were treated with Ad.Luc, Ad.Bax, Ad.IL-24 or Ad.IL-24-Bax (MOI=10) for 72 h. Cells were harvested for Annexin V-fluorescein isothiocyanate/proliferation index staining analysis.
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fig3: Ad.IL-24-Bax suppressed the proliferation of hepatocellular carcinoma cells and induced apoptosis in hepatocellular carcinoma in vitro. (a) Cell viability after Ad.IL-24-Bax treatment by methyl thiazolyl tetrazolium assays. Normal hepatocyte (L02) and hepatocellular carcinoma cells (HepG2, Hep3B, PLC/PRF/5) were treated with Ad.Luc (◊), Ad.Bax (), Ad.IL-24 (▴) or Ad.IL-24-Bax (▪) at different multiplicities of infection (MOI). Three days after infection, the cell survival rate was checked. Ad.IL-24-Bax inhibited hepatocellular carcinoma cell growth, while having little influence on the growth of normal liver cells. (b) Percentage of apoptotic cells after Ad.IL-24-Bax treatment using the Annexin V-fluorescein isothiocyanate/proliferation index staining method. Normal hepatocytes (L02) and hepatocellular carcinoma cells (HepG2, Hep3B, PLC/PRF/5) were treated with Ad.Luc, Ad.Bax, Ad.IL-24 or Ad.IL-24-Bax (MOI=10) for 72 h. Cells were harvested for Annexin V-fluorescein isothiocyanate/proliferation index staining analysis.

Mentions: Figure 3a illustrated the cell viability of Hep3B, PLC/PRF/5, HepG2 and L02 cells after transfection with the recombinant adenovirus at different MOIs. When transfected and cultured with Ad.IL-24 and Ad.IL-24-Bax at high MOI, the growth of hepatocellular carcinoma cells was significantly inhibited. When the MOI was >10, the survival rate of hepatocellular carcinoma cells was significantly lower when transfected and cultured with Ad.IL-24-Bax than with Ad.IL-24 (P<0.05). Meanwhile, the growth curve of normal hepatocyte L02 was not significantly changed (P>0.05) when transfected and cultured with Ad.Bax, Ad.IL-24 or Ad.IL-24-Bax. When transfected and cultured with Ad.Luc, the growth curves of normal hepatocytes and hepatocellular carcinoma cells were similar.


Recombinant adenovirus IL-24-Bax promotes apoptosis of hepatocellular carcinoma cells in vitro and in vivo.

Li J, Shi L, Zhang X, Kang X, Wen Y, Qian H, Zhou Y, Xu W, Zhang Y, Wu M, Yin Z - Cancer Gene Ther. (2010)

Ad.IL-24-Bax suppressed the proliferation of hepatocellular carcinoma cells and induced apoptosis in hepatocellular carcinoma in vitro. (a) Cell viability after Ad.IL-24-Bax treatment by methyl thiazolyl tetrazolium assays. Normal hepatocyte (L02) and hepatocellular carcinoma cells (HepG2, Hep3B, PLC/PRF/5) were treated with Ad.Luc (◊), Ad.Bax (), Ad.IL-24 (▴) or Ad.IL-24-Bax (▪) at different multiplicities of infection (MOI). Three days after infection, the cell survival rate was checked. Ad.IL-24-Bax inhibited hepatocellular carcinoma cell growth, while having little influence on the growth of normal liver cells. (b) Percentage of apoptotic cells after Ad.IL-24-Bax treatment using the Annexin V-fluorescein isothiocyanate/proliferation index staining method. Normal hepatocytes (L02) and hepatocellular carcinoma cells (HepG2, Hep3B, PLC/PRF/5) were treated with Ad.Luc, Ad.Bax, Ad.IL-24 or Ad.IL-24-Bax (MOI=10) for 72 h. Cells were harvested for Annexin V-fluorescein isothiocyanate/proliferation index staining analysis.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2963730&req=5

fig3: Ad.IL-24-Bax suppressed the proliferation of hepatocellular carcinoma cells and induced apoptosis in hepatocellular carcinoma in vitro. (a) Cell viability after Ad.IL-24-Bax treatment by methyl thiazolyl tetrazolium assays. Normal hepatocyte (L02) and hepatocellular carcinoma cells (HepG2, Hep3B, PLC/PRF/5) were treated with Ad.Luc (◊), Ad.Bax (), Ad.IL-24 (▴) or Ad.IL-24-Bax (▪) at different multiplicities of infection (MOI). Three days after infection, the cell survival rate was checked. Ad.IL-24-Bax inhibited hepatocellular carcinoma cell growth, while having little influence on the growth of normal liver cells. (b) Percentage of apoptotic cells after Ad.IL-24-Bax treatment using the Annexin V-fluorescein isothiocyanate/proliferation index staining method. Normal hepatocytes (L02) and hepatocellular carcinoma cells (HepG2, Hep3B, PLC/PRF/5) were treated with Ad.Luc, Ad.Bax, Ad.IL-24 or Ad.IL-24-Bax (MOI=10) for 72 h. Cells were harvested for Annexin V-fluorescein isothiocyanate/proliferation index staining analysis.
Mentions: Figure 3a illustrated the cell viability of Hep3B, PLC/PRF/5, HepG2 and L02 cells after transfection with the recombinant adenovirus at different MOIs. When transfected and cultured with Ad.IL-24 and Ad.IL-24-Bax at high MOI, the growth of hepatocellular carcinoma cells was significantly inhibited. When the MOI was >10, the survival rate of hepatocellular carcinoma cells was significantly lower when transfected and cultured with Ad.IL-24-Bax than with Ad.IL-24 (P<0.05). Meanwhile, the growth curve of normal hepatocyte L02 was not significantly changed (P>0.05) when transfected and cultured with Ad.Bax, Ad.IL-24 or Ad.IL-24-Bax. When transfected and cultured with Ad.Luc, the growth curves of normal hepatocytes and hepatocellular carcinoma cells were similar.

Bottom Line: The mechanism of this response may include the effect of the 10HRE/VEGF385 promoter and the synergistic effect of IL-24 and Bax.Ad.IL-24-Bax also suppressed tumor growth in nude mice and induced apoptosis.Ad.IL-24-Bax may be a useful tool for gene therapy of hepatic cancer.

View Article: PubMed Central - PubMed

Affiliation: Molecular Oncology Laboratory, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.

ABSTRACT
Gene therapy promises to become an alternative choice for the treatment of hepatic cancer. In many cancers, the delivery of chimeric proteins by adenovirus vector has been reported to induce apoptosis. This study was performed to evaluate whether the recombinant adenovirus interleukin (IL)-24-Bax can induce apoptosis in hepatocellular carcinoma cells in vitro and in vivo. Several recombinant adenoviruses were constructed, and the expression of their encoded proteins was measured. The effects of the recombinant adenovirus on hepatocellular carcinoma cells and the normal hepatocyte cell line were investigated through cell viability and apoptosis assays after the cells were treated with Ad.Luc, Ad.IL-24, Ad.Bax or Ad.IL-24-Bax. The mechanism involved was also explored. A tumor-bearing mouse model was used to evaluate the effects of the adenovirus on tumor volume and cell apoptosis in vivo. Ad.IL-24-Bax selectively suppressed growth of hepatocellular carcinoma cells and induced apoptosis, but it had little influence on the normal hepatocytes. The mechanism of this response may include the effect of the 10HRE/VEGF385 promoter and the synergistic effect of IL-24 and Bax. Ad.IL-24-Bax also suppressed tumor growth in nude mice and induced apoptosis. Ad.IL-24-Bax may be a useful tool for gene therapy of hepatic cancer.

Show MeSH
Related in: MedlinePlus