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Archive > Volume 29 Issue 4 > 2022,29(4):301-307. DOI:10.3872/j.issn.1007-385X.2022.04.005 Prev Next
Basic Research
Efficacy and safety of recombinant Bifidobacterium breve carrying HPV16 E7 shRNAand IL-12 gene against mouse cervical cancer xenografts
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Abstract:
Objective: To evaluate the effect of oral administration of recombinant Bifidobacterium breve (B.breve) carrying HPV16 E7 shRNA and IL-12 gene in mice against cervical cancer xenografts. Methods: pMG36e-E7 shRNA and pMG36e-mIL-12D plasmids were used to modify the B.breve. After screening, verification and amplification, recombinant B.breve carrying HPV16 E7 shRNA and IL-12 gene were obtained. Tumor-bearing mouse model was established by subcutaneously injecting cervical cancer cells. On the 1st and 7th day after oral administration, the tumor-targeting property of recombinant B.breve were evaluated by counting the number of bacteria colonies formed in the homogenate of mouse major organs (heart, liver, spleen, lung and kidney) and tumor tissues or serum that cultured in PYG medium. The antitumor effect of recombinant B.breve was evaluated by in vivo tumor growth curve. The safety of oral administration of recombinant B.breve was evaluated by H-E staining of the tissue sections from major organs and determination of the levels of related cytokines in serum of tumor-bearing mice. Results: Recombinant B.breve and cervical TC-1 cell transplanted tumor bearing mice were successfully established. After 7 days, the number of colonies in the homogenate of tumor tissues and serum confirmed that recombinant B.breve had the property of targeting tumor tissues in vivo. Oral administration of recombinant B.breve significantly suppressed tumor growth in tumor-bearing mice (P<0.05 or P<0.01); however, there was no significant difference in tumor inhibition rate between the recombinant B.breve carrying both HPV16 E7 shRNA and IL-12 gene and those carrying single one. After the treatment, no major organ damage or significant changes in serum IL-12 and IFN-γ levels was observed in tumor-bearing mice. Conclusion: B. breve can be used as a safe and controllable therapeutic molecular delivery vehicle for targeting tumors, which exert significant treatment efficacy against cervical cancer xenografts.
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Clc Number:
Q789；R737.33；R730.54
