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Adam M Luchey md Division of Urology, Department of Surgery West Virginia University

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 M Luchey md Division of Urology, Department of Surgery West Virginia University

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Adam M Luchey md Division of Urology, Department of Surgery West Virginia University

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  1. 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 M Luchey md • Division of Urology, Department of Surgery • West Virginia University • Dale Riggs, Barbara Jackson, Can Talug, Stanley Kandzari, Dana Point, and Stanley Zaslau

  2. Prostate Cancer • Prostate cancer is the most common internal tumor in US males and second leading cause of cancer death • Initial treatments are surgery (open, laparoscopic, robotic), brachytherapy & external beam radiation • Further treatment is based on PSA (Prostate Specific Antigen) • If elevated (biochemical recurrence), treatment is either radiation or hormonal therapy

  3. Androgen Deprivation • Lutenizing Hormone Releasing Hormone (LHRH) agonists • Leads to decrease in FSH and LH • Leuprolide, Gosrelin • Androgen Synthesis Inhibitors • Ketoconazole • Aminoglutethimide • Nonsteroidal Antiandrogens • Libido and Potency preserved • Steroidal Antiandrogens • Surgery

  4. Castrate-Resistant Prostate Cancer • Formally known as Hormone-Resistant Prostate Cancer • On average occurs in 2 years • Add additional agents • Antiandrogen • Surgical castration • Chemotherapy • Docetaxel regimen • Only prolongs survival 16-18 months • Myelosuppresion, Neurotoxicity, and fatigue • Can it be combined to improve its use?

  5. IP-6 • Inositol-Hexaphosphate is a polyphosphorylated carbohydrate found in legumes and cereals that are high in fiber • Shown to disrupt the growth of (in vivo and in vitro) numerous cancer lines (breast, pancrease, prostate, melanoma) • We have previously shown its inhibitory effect through induction of apoptosis/necrosis and as an inhibitor of VEGF and GI bladder cancer cell lines • Can this be combined with docetaxel to improve its effect and limit its side effects?

  6. Project Design • PC3 and DU-145 • Castrate-Resistant Prostate Cancer Cell Lines • Both were cultured with IP-6 (0.25 and 0.5 mM/well) and/or Docetaxel (2.5 and 5 nM/well) • Cell Viability determined at 24, 48, and 72 hours using MTT assay • Statistical analysis preformed via ANOVA and individual comparisons by the Tukey Test

  7. Results

  8. Conclusions • When combined, Docetaxel and IP-6 have an additive effect causing increase in cell kill • With IP-6, a dose of 2.5 nM of Docetaxel had more of an effect than a dose of 5.0 nM • More effective and less toxic • Need to further delineate IP-6 action • Necrosis/Apoptosis • Cell cycle inhibition • In vitro to in vivo studies

  9. Questions

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