the in vitro anti-tumor activity of docetaxel in combination with inositol hexaphosphate (ip-6) in...
TRANSCRIPT
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 mdDivision of Urology, Department of Surgery
West Virginia University
Dale Riggs, Barbara Jackson, Can Talug, Stanley Kandzari, Dana Point, and Stanley Zaslau
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
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
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?
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?
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
Results
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
Questions