Aim: DES results in PSA response rates of up to 50% in patients refractory to first line hormonal therapy. The modulation of the IGF axis appears important in the transition to androgen independent disease and there is potential crosstalk between the ER and IGF-axis during tumor progression to the androgen independent state. We therefore hypothesized that DES will work synergistically with IGF-1 antibodies to inhibit prostate cancer growth. Methods: PC-3 prostate cancer cells were treated with DES, ketoconazole, IGF-1 antibody both alone and in various combinations. The effect on proliferation was assessed using the MTT assay. Additionally, the apoptotic effect on the Bax/BCl-2 ratio was then evaluated using Western Blot analysis. Results: The proliferation of logarithmically growing PC-3 cells was analyzed by the MTT quantitative colorimetric assay. The statistical analysis showed a significant inhibitory effect with the combination of DES and the IGF-1 which was greater than any other single agent or combination effect. Also, the IGF-1 antibody induced the Bax/Bcl-2 ratio favorably in combination with either DES or ketoconazole compared to each single agent. Conclusion: DES and anti-IGF-1 antibody synergistically inhibit the growth of PC-3 prostate cancer cells in vitro. Further testing of the in vivo effects and mechanism of action of this promising combination is warranted.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 827.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

American Association for Cancer Research
2009