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A novel Bifidobacterium infantis-mediated TK/GCV suicide gene therapy system exhibits antitumor activity in a rat model of bladder cancer.

Tang W, He Y, Zhou S, Ma Y, Liu G - J. Exp. Clin. Cancer Res. (2009)

Bottom Line: Successful clinical management remains a challenge.The engineered BI-TK was injected into tumor-bearing rats via tail vein, followed by intraperitoneal injection of ganciclovir (GCV).Immunohistochemical staining further demonstrated that the BI-TK/GCV treatment group had the highest level of caspase3 protein expression than that of the empty plasmid group and normal saline group (p < 0.05).

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Urology, First Affiliated Hospital, Chongqing Medical University, Chongqing, China. tangwei2060@yahoo.com.cn

ABSTRACT
Bladder cancer is the ninth most common malignancy in the world. Successful clinical management remains a challenge. In order To search for novel targeted and efficacious treatment, we sought to investigate anti-tumor activity of BI-TK suicide gene therapy system in a rat model of bladder tumors. We first constructed and tested an anaerobic Bifidobacterium infantis-mediated thymidine kinase (BI-TK) suicide gene therapy system. To test the in vivo efficacy of this system, we established a rat model of bladder tumors, which was induced by N-methyl-nitrosourea perfusion. Bifidobacterium infantis containing the HSV-TK (i.e., BI-TK) were constructed by transformation of recombinant plasmid pGEX - TK. The engineered BI-TK was injected into tumor-bearing rats via tail vein, followed by intraperitoneal injection of ganciclovir (GCV). Using the rat model of bladder tumors, we found that bladder tumor burdens were significantly lower in the rats treated with BI-TK/GCV group than that treated with normal saline control group (p <0.05). While various degrees of apoptosis of the tumor cells were detected in all groups using in situ TUNEL assay, apoptosis was mostly notable in the BI-TK/GCV treatment group. Immunohistochemical staining further demonstrated that the BI-TK/GCV treatment group had the highest level of caspase3 protein expression than that of the empty plasmid group and normal saline group (p < 0.05). Thus, our results demonstrate that the Bifidobacterium infantis-mediated TK/GCV suicide gene therapy system can effectively inhibit rat bladder tumor growth, possibly through increasing caspase 3 expression and inducing apoptosis.

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Apoptosis analysis of BI-TK/GCV treated rat bladder cancer. The TUNEL assay was carried out as described in Methods. Cells with positive staining were randomly counted in 10 high-power fields and the apoptosis index was calculated (mean SD). (A) Normal saline group (6.88 ± 1.40), (B) Bifutobacterium infantis with empty plasmid group (16.01 ± 3.48), and (C) Bifutobacterium infantis-PGEX-TK group (41.72 ± 4.27). There is statistically significant difference between each groups (p < 0.05). Representative samples are shown. Magnification, 100×.
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Figure 3: Apoptosis analysis of BI-TK/GCV treated rat bladder cancer. The TUNEL assay was carried out as described in Methods. Cells with positive staining were randomly counted in 10 high-power fields and the apoptosis index was calculated (mean SD). (A) Normal saline group (6.88 ± 1.40), (B) Bifutobacterium infantis with empty plasmid group (16.01 ± 3.48), and (C) Bifutobacterium infantis-PGEX-TK group (41.72 ± 4.27). There is statistically significant difference between each groups (p < 0.05). Representative samples are shown. Magnification, 100×.

Mentions: Using the in situ TUNEL method, we found that each group exhibted varying degrees of apoptosis-staining positivity (Figure 3). The apoptotic indexes were 14.33 ± 5.29% for the NS group, 15.50 ± 4.34% for BI-pGEX-5X-1 group, and 29.44 ± 6.64% for BI-TK group, respectively. The apoptotic index for BI-TK group was significantly higher than that of BI-pGEX-5X-1 group or the NS group (p <0.05). These results indicate that BI-TK/GCV suicide gene therapy system can kill bladder cancer cells, possibly through inducing apoptosis.


A novel Bifidobacterium infantis-mediated TK/GCV suicide gene therapy system exhibits antitumor activity in a rat model of bladder cancer.

Tang W, He Y, Zhou S, Ma Y, Liu G - J. Exp. Clin. Cancer Res. (2009)

Apoptosis analysis of BI-TK/GCV treated rat bladder cancer. The TUNEL assay was carried out as described in Methods. Cells with positive staining were randomly counted in 10 high-power fields and the apoptosis index was calculated (mean SD). (A) Normal saline group (6.88 ± 1.40), (B) Bifutobacterium infantis with empty plasmid group (16.01 ± 3.48), and (C) Bifutobacterium infantis-PGEX-TK group (41.72 ± 4.27). There is statistically significant difference between each groups (p < 0.05). Representative samples are shown. Magnification, 100×.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2803447&req=5

Figure 3: Apoptosis analysis of BI-TK/GCV treated rat bladder cancer. The TUNEL assay was carried out as described in Methods. Cells with positive staining were randomly counted in 10 high-power fields and the apoptosis index was calculated (mean SD). (A) Normal saline group (6.88 ± 1.40), (B) Bifutobacterium infantis with empty plasmid group (16.01 ± 3.48), and (C) Bifutobacterium infantis-PGEX-TK group (41.72 ± 4.27). There is statistically significant difference between each groups (p < 0.05). Representative samples are shown. Magnification, 100×.
Mentions: Using the in situ TUNEL method, we found that each group exhibted varying degrees of apoptosis-staining positivity (Figure 3). The apoptotic indexes were 14.33 ± 5.29% for the NS group, 15.50 ± 4.34% for BI-pGEX-5X-1 group, and 29.44 ± 6.64% for BI-TK group, respectively. The apoptotic index for BI-TK group was significantly higher than that of BI-pGEX-5X-1 group or the NS group (p <0.05). These results indicate that BI-TK/GCV suicide gene therapy system can kill bladder cancer cells, possibly through inducing apoptosis.

Bottom Line: Successful clinical management remains a challenge.The engineered BI-TK was injected into tumor-bearing rats via tail vein, followed by intraperitoneal injection of ganciclovir (GCV).Immunohistochemical staining further demonstrated that the BI-TK/GCV treatment group had the highest level of caspase3 protein expression than that of the empty plasmid group and normal saline group (p < 0.05).

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Urology, First Affiliated Hospital, Chongqing Medical University, Chongqing, China. tangwei2060@yahoo.com.cn

ABSTRACT
Bladder cancer is the ninth most common malignancy in the world. Successful clinical management remains a challenge. In order To search for novel targeted and efficacious treatment, we sought to investigate anti-tumor activity of BI-TK suicide gene therapy system in a rat model of bladder tumors. We first constructed and tested an anaerobic Bifidobacterium infantis-mediated thymidine kinase (BI-TK) suicide gene therapy system. To test the in vivo efficacy of this system, we established a rat model of bladder tumors, which was induced by N-methyl-nitrosourea perfusion. Bifidobacterium infantis containing the HSV-TK (i.e., BI-TK) were constructed by transformation of recombinant plasmid pGEX - TK. The engineered BI-TK was injected into tumor-bearing rats via tail vein, followed by intraperitoneal injection of ganciclovir (GCV). Using the rat model of bladder tumors, we found that bladder tumor burdens were significantly lower in the rats treated with BI-TK/GCV group than that treated with normal saline control group (p <0.05). While various degrees of apoptosis of the tumor cells were detected in all groups using in situ TUNEL assay, apoptosis was mostly notable in the BI-TK/GCV treatment group. Immunohistochemical staining further demonstrated that the BI-TK/GCV treatment group had the highest level of caspase3 protein expression than that of the empty plasmid group and normal saline group (p < 0.05). Thus, our results demonstrate that the Bifidobacterium infantis-mediated TK/GCV suicide gene therapy system can effectively inhibit rat bladder tumor growth, possibly through increasing caspase 3 expression and inducing apoptosis.

Show MeSH
Related in: MedlinePlus