Objective: To investigate the effect of inositol hexaphosphate (IP6) on proliferation of human prostate carcinoma LNCaP cells and its relation to insulin-like growth factors binding protein-3 (IGFBP-3) expression. Methods: The siRNA technology was used to silence the IGFBP-3 gene in LNCaP cells. LNCaP cells and IGFBP3 gene silenced LNCaP cells were exposed to IP6 for 24 h. Cell viability was measured by MTT assay; cell cycle arrest and cell apoptosis were detected by flow cytometry. The expression levels of IGFBP-3 and Bcl-2 mRNA and protein were analyzed by real-time quantitative RT-PCR and Western blotting,  respectively. Results: The proliferation of LNCaP cells was be inhibited by IP6 in a dose-dependent manner. After exposure to IP6 for 24 h, the cell viability in LNCaP cells and siRNA-treated LNCaP cells was 53.2%±11.6% and 82.3%±10.9% , respectively (P<0.05). After treatment of 1.5 mmol IP6, the apoptosis rate of LNCAP cells and siRNA-treated LNCAP cells was 40.48%±13.21% and 30.43%±10.65%, respectively(P<0.05). The proportion of G1 and G2 phase in LNCAP cells was 70.58%±8.25% and 5.64%±1.23%, after IP6 treatment the percentage of G₁ phase cells decreased to 48.66%±11.23% and G2 phase cells increased to 31.11%±9.68%. However, for siRNA treated LNCAP cells  the proportion of G₁ phase cells was 58.25%±12.36% and G₂ phase cells was 23.85%±12.45%. Higher expression

of IGFBP-3 and lower expression of Bcl-2 in LNCaP cells treated with IP6 were found at both mRNA and protein levels. IP6 treatment enhanced IGFBP-3 mRNA

expression by 2.21±0.15 folds. In the contrast, expression of Bcl-2 mRNA decreased by 0.69±0.03 folds. Meanwhile, after IGFBP-gene silence Bcl-2 expression was not decreased. Conclusion: IP6 can inhibit the proliferation of LNCaP cells, which may be associated with the changes of IGFBP-3 level through Bcl-2

expression.