Figure 5. GnRH agonists resensitize p53-positive DU145 cells to the cytotoxic activity of docetaxel.

DU145 prostate cancer cells were made resistant to docetaxel (Doc) after treatment with the chemotherapeutic drug (10 nmol/L) once a week for 8 cycles. (A) Western blot analysis of Bcl-2 and Bax in docetaxel-resistant (DU145-R) cells. In DU145-R cells the expression of the proapoptotic protein Bax looks significantly down-regulated, while the expression of the antiapoptotic protein Bcl-2 is not significantly modulated. One representative of three different experiments is shown. Data represent means ± SEM. *P<0.05 versus DU145 cells. (B) Clonogenic survival assay of DU145-R cells pretreated with GnRH-A (10⁻⁶ mol/L) for 24 hours and then treated with docetaxel (10 nmol/L) for 72 hours. GnRH-A given alone does not affect the ability of DU145-R cells to form colonies. DU145-R cells can form colonies in the presence of the chemotherapeutic agent, confirming their acquisition of resistance to the drug. Combination treatment completely abolishes the colony formation ability of DU145-R cells. Each experimental group consisted of two/three replicates and each experiment was repeated three times with identical results.