Objective: To evaluate the in vivo therapeutic effects of attenuated Salmonella carrying PCDNA3.1-ERβ plasmid in hormone-independent prostatic cancer in nude mice and to clarify the mechanism by which estrogen receptor β (ERβ) induces apoptosis and proliferation in prostatic cancer cells in mice.
Methods: The orthotopic prostatic cancer models of mice were randomly divided as follows: MOCK group, treated with PBS, PQ group, treated with attenuated Salmonella alone, PQ-PCDNA3.1 group, treated with attenuated Salmonella carrying PCDNA3.1 plasmid, and PQ-PCDNA3.1-ERβ group, treated with the attenuated Salmonella carrying PCDNA3.1-ERβ plasmid. Then, 10 μl of the plasmid-containing solution, comprising 1 × 107 cfu of the bacteria, was administered via intranasal delivery to each group except the MOCK group. The experimental methods included flow cytometry and terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL) assay, immunohistochemistry, and western blotting.
Results: Compared with the MOCK, PQ, and PQ-PCDNA3.1 groups, the weights of tumors in the PQ-PCDNA3.1-ERβ group were significantly reduced. The results of flow cytometry and TUNEL assay revealed that the number of apoptotic cells in the PQ-PCDNA3.1-ERβ group significantly increased. Compared with PQ-PCDNA3.1 group, the protein expression levels of ERβ, Bad, p-caspase 9, p-caspase 3, and cleaved PARP in the PQ-PCDNA3.1-ERβ group were significantly increased, while the expression levels of Akt, p-Akt, and Bcl-xl were decreased (P < 0.05).
Conclusion: The attenuated Salmonella carrying PCDNA3.1-ERβ plasmid could inhibit the growth of orthotopic prostatic cancer in mice by increasing the expression of ERβ.