Antitumor effect of small interfering RNA targeting ALKBH3 gene on human prostate cancer xenograft in nude mice

Objective To investigate the antitumor effect of small interfering RNA (siRNA)-mediated inhibition of ALKBH3 gene expression on nude mice xenograft with human prostate cancer cell,and to explore its mechanism of action.Methods The nude mice model of human prostate cancer was established by injecting human LNCaP cells subcutaneously.The ALKBH3-siRNA was injected into the tumor of experiment group.Terminal deoxynucleotidyl transferase-mediated nicked labeling assay (TUNEL) was undertaken to detect the cell apoptosis in the tumor tissue.Immunohistochemistry (IHC) and Western blotting was used to detect the expression of ALKBH3,proliferating cell nuclear antigen (PCNA) and B cell lymphoma/leukemia-2 (bcl-2).Results The tumor growth of experiment group was slower than that of the other two groups (P ＜ 0.05).The integrated optical density (IA) of the experimental group (6 558.2 ± 1 567.1) was significantly higher than that of the other two groups (460.2 ±203.5 and 588.5 ± 241.3,all P ＜0.05).Immunohistochemistry showed that the expression level of ALKBH3 in experimental group (0.26 ± 0.03) were lower than the blank group (0.43 ± 0.07) and control group (0.48 ± 0.06,P ＜ 0.05),the expression level of PCNA protein in the experimental group (0.16 ± 0.02) were lower than the control group (0.28 ± 0.05) and control group (0.31 ± 0.05,all P ＜ 0.05),the expression level of bcl-2 in experimental group (0.31 ±0.05) were lower than the blank group (0.55 ±0.12) and the control group (0.49 ± 0.11,all P ＜ 0.05).Conclusion SiRNA targeting ALKBH3 gene could inhibit obviously the tumor growth by inducing apoptosis in human prostate cancer xenograft in nude mice.Its mechanism of action is possibly related with the downregulation of PCNA and bcl-2 expression. Key words: Prostate cancer;  ALKBH3;  RNA interfering