Abstract
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.
Highlights
Estrogen is an important hormone in humans
Cancer-bearing mice were intranasally given either PBS, attenuated Salmonella alone, attenuated Salmonella carrying PCDNA3.1 plasmid, or attenuated Salmonella carrying PCDNA3.1-estrogen receptor β (ERβ) plasmid, which was repeated on day 10
A significant difference was observed between the mean body weight and mean tumor weight of the mice in the MOCK, PQ, and PQ-PCDNA3.1 groups and that of mice in the PQ-PCDNA3.1-ERβ group (P < 0.05)
Summary
Estrogen is an important hormone in humans. Studies have shown that estrogen signaling plays a significant role in the normal and abnormal growth of the prostate gland [1, 2]. In 1996, the discovery of estrogen receptor beta (ERβ) in rats [3] and humans [4] changed our understanding of the estrogen signaling. The effects of estrogen on target tissues are known to be mediated by estrogen receptor alpha (ERα) and ERβ, which are members of the nuclear hormone receptor family and ligand-activated transcription factors. Expression of estrogen receptors has been found in many other tumors such as breast, uterus, ovarian, colon, and prostate and identified in bladder, lung cancer, and so on [5, 6]. The human prostate is equipped with a dual system of ERs: ERα and ERβ, and they undergo significant remodeling in the process of prostate cancer (PCa) development and progression [7,8,9]. There is growing evidence showing that ERβ is gradually lost in cancer progression
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