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The In Vitro Anti-tumor Activity of Docetaxel in Combination with Inositol Hexaphosphate (IP-6) in Castrate-Resistant PC3 and DU-145 Prostate Cancer Cell Lines
Adam Luchey, Can Talug, Dale Riggs, Barbara Jackson, Dana Point, Stanley Zaslau, Stanley Kandzari
West Virginia University, Morgantown, WV

Introduction: Inositol Hexaphosphate (IP-6) regulates the cell cycle, apoptosis, and cellular proliferation in prostate cancer lines in vitro. We hypothesized that when combined with Docetaxel (DOC), IP-6 Results in an additive reduction in cellular proliferation in castrate-resistant prostate cancer cell lines (CPCL), PC3 and DU-145, thereby increasing effectiveness and minimizing toxicity of DOC.
Materials & Methods: PC3 and DU-145 CPCL were cultured using standard techniques and incubated with IP-6 (0.25 and 0.5mM/well) and/or DOC (2.5 and 5nM/well). Cell viability was measured by MTT at 24, 48 and 72 hours thereafter. Statistical analysis was performed by ANOVA, with individual comparisons made by the Tukey test.
Results: Significant reductions (P<0.001) in cellular growth were noted in both cell lines and at all time frames with the combination of DOC and IP-6 compared to control. At 24 hours with DU-145, there was significance in kill rate with the combination of DOC 5nM/IP-6 0.5mM versus each agent alone (P<0.001), but not with PC3. At 48 and 72 hours with PC3, but not DU-145, the combinations of DOC 2.5nM/IP-6 0.25mM produced significantly higher kill rates than DOC 5mM (P<0.001).

: When combined, DOC and IP-6 exhibited an additive reduction in cellular proliferation in both CPCL. IP-6, when combined with DOC 2.5nM, achieved a significant reduction in cellular proliferation equal to that observed with DOC 5.0nM. These Results indicate that a lower dose of DOC with IP-6 could potentially lead to a more effective and less toxic treatment for castrate-resistant prostate cancer and warrants further investigation.

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