Bid sensitizes apoptosis induced by chemotherapeutic drugs in hepatocellular carcinoma

Jiang, Miao; Chen, George G; Chun, Sukying; Chak, Ernest C.W.; Lai, Paul Bo San

doi:10.3892/ijo.25.3.651

Cited by 20 publications

(50 citation statements)

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“…[11][12][13][14] Our previous in vitro study showed that the application of Ad/AFPtBid specifically killed Hep3B cells that are known to produce AFP, and significantly sensitized Hep3B cells to 5-FU and Dox. 20,21 In this study, we confirmed that Ad/AFPtBid could specifically suppress the AFP-producing HCC but not attack non-AFP-producing tumor in an orthotopic mouse model. Application of Ad/AFPtBid can significantly increase the effect of other chemotherapeutic agents such as 5-FU, resulting in a synergistic interaction between Ad/AFPtBid and 5-FU in our model.…”

Section: Discussionsupporting

confidence: 71%

“…Furthermore, over-expression of Bid especially tBid significantly sensitized Hep3B cells to two commonly used HCC chemotherapeutic agents 5-fluorouracil (5-FU) and doxorubicin (Dox) in vitro. 20,21 It appears that the combination of gene therapy with existing chemotherapy or radiotherapy is likely to be more effective than separate approach alone. 22,23 The objective of this study is to test therapeutic efficacy of Ad/AFPtBid or its combination with 5-FU or Dox in an orthotopic hepatic tumor model, which represents naturally occurring HCC.…”

Section: Introductionmentioning

confidence: 99%

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Therapeutic effect of α-fetoprotein promoter-mediated tBid and chemotherapeutic agents on orthotopic liver tumor in mice

Chen

Yip

et al. 2010

Gene Ther

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Previous studies have shown that the application of Ad/AFPtBid significantly and specifically killed hepatocellular carcinoma (HCC) cells in culture and subcutaneously implanted in mice. This study was to test the therapeutic efficacy of Ad/AFPtBid in an orthotopic hepatic tumor model. Four weeks after implantation of tumor cells into the liver, nude mice were treated with Ad/ AFPtBid alone or in combination with 5-fluorouracil (5-FU). Serum a-fetoprotein (AFP) was measured as a marker for tumor progression. The results showed that Ad/AFPtBid significantly inhibited Hep3B tumor growth. Ad/AFPtBid and 5-FU in combination was more effective than either agent alone. Tumor tissues of Ad/AFPtBid alone or combination treatment groups showed a decrease in cells positive for proliferation cell nuclear antigen, but an increase in apoptosis. Ad/AFPtBid did not suppress the hepatic tumor formed by non-AFP-producing hepatoma SK-HEP-1 cells or colorectal adenocarcinoma DLD-1 cells. The survival rate was higher in mice treated with Ad/AFPtBid plus 5-FU than those treated with either agent alone. No acute toxic effect was observed in mice receiving Ad/AFPtBid. Collectively, Ad/AFPtBid can specifically target and effectively suppress the AFP-producing orthotopic liver tumor in mice without obvious toxicity, indicating that it is a promising tool in combination with chemotherapeutic agents for treatment of AFP-producing HCC.

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Section: Discussionsupporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Therapeutic effect of α-fetoprotein promoter-mediated tBid and chemotherapeutic agents on orthotopic liver tumor in mice

Chen

Yip

et al. 2010

Gene Ther

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“…We have shown that the expression and the regulation of BH3-only protein Bid play crucial roles in HCC tumorigenesis and in response to chemotherapeutic treatment [20][21][22]. However, to the best of our knowledge, the characterization of Bim and its isoforms in HCC has not been studied before.…”

Section: Introductionmentioning

confidence: 92%

“…To establish mammalian expression constructs, plasmids with various inserts (Bim isoforms) were selected and digested with EcoRI, and then sub-cloned into a mammalian expression vector pcDNA3.1, generating p3.1/Bim EL, p3.1/Bim L, etc. The construction of plasmids p3.1/Bid and p3.1/tBid has been described in our previous study [21].…”

Section: Agilent Bioanalyzer 2100mentioning

confidence: 99%

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Identification and characterization of BH3 domain protein Bim and its isoforms in human hepatocellular carcinomas

et al. 2007

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BH3-only protein Bim is a critical regulator of apoptosis and plays an essential role in mammalian development, but the characterization of Bim and its isoforms in hepatocellular carcinoma (HCC) has not been studied before. Here we investigated the expression, distribution, regulation and role of Bim isoforms in HCC cells. Fifteen Bim isoforms were identified in HCC, with six newly identified isoforms and two newly identified exons. Among of them, Bim EL, L, S, a1, a2, a3, b2, b4 and b6 are abundant isoforms according to their mRNA levels. However only Bim EL, L and S proteins could be clearly detected. Bim mRNA and protein were strongly expressed in HCC tissues compared to relevant non-tumorous regions, but the ratio of variant isoforms showed no difference between tumorous and non-tumorous tissues. Bim isoforms were differentially regulated after chemotherapeutic drug 5-Fluorouracil (5-FU) treatment. Interestingly, Bim EL, L and S, the isoforms known to induce apoptosis strongly, are the least inducible isoforms at their mRNA levels when exposed to the stress, suggesting that post-transcriptional rather than transcriptional, modulations may play a role to enhance their functions. Finally, overexpression of Bim EL, L, S and all alpha isoforms induced apoptosis in HCC cells, while overexpression of Bim beta isoforms showed no effects on cell survival after 5-FU treatment. In conclusion, Bim alpha isoforms appears to have a role in the regulation of apoptosis in HCC cells, which may contribute to not only the growth of tumor cells but also the sensitivity of HCC cells to chemotherapy.

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Hoxa2 plays a direct role in murine palate development

Smith

Wang

Zhang

et al. 2009

Developmental Dynamics

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The cleft palate exhibited by Hoxa2 null murine embryos has been described as being secondary to abnormalities of tongue musculature, and Hoxa2 was presumed to not play a direct role in palate development. However, we detected Hoxa2 expression in the developing palate at both the mRNA and protein levels between embryonic day (E) 12.5 and E15.5. Organ cultures of Hoxa2 ؊/؊ palates maintained in the absence of the tongue showed decreased fusion rates than either Hoxa2 ؉/؊ or Hoxa2 ؉/؉ palate cultures. Knocking down Hoxa2 expression with antisense retroviral constructs resulted in decreased fusion rates than corresponding controls. An overall increase in cell proliferation was observed in Hoxa2 null palates providing a potential mechanism by which Hoxa2 may be affecting palate development. Hoxa2 also repressed the expression of its downstream targets Msx1, Bmp4, Barx1, and Ptx1 within the palate. These results demonstrate the cleft palate phenotype of Hoxa2 null embryos is not solely due to abnormal tongue musculature, and indicate a direct role of Hoxa2 in regulating murine palatogenesis. Developmental Dynamics 238:2364 -2373, 2009.

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Bid sensitizes apoptosis induced by chemotherapeutic drugs in hepatocellular carcinoma

Cited by 20 publications

References 0 publications

Therapeutic effect of α-fetoprotein promoter-mediated tBid and chemotherapeutic agents on orthotopic liver tumor in mice

Therapeutic effect of α-fetoprotein promoter-mediated tBid and chemotherapeutic agents on orthotopic liver tumor in mice

Identification and characterization of BH3 domain protein Bim and its isoforms in human hepatocellular carcinomas

Hoxa2 plays a direct role in murine palate development

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