Expression of anti-apoptosis genes determines the response of adrenal cancer to apoptosis-inducing chemotherapy.

Background: This study tested the hypothesis that response of adrenal cortical carcinoma (ACC) to proapoptosis drugs depends on expression of anti-apoptosis genes. Materials and Methods: Expression of Bcl-2 and Bcl-XL proteins was determined in two human adrenal cancer cell lines, NCI-H-295 and RL-251. Two pro-apoptosis drugs, gossypol (G) and docetaxel (D) were tested in vitro and in vivo in a human ACC/SCID mouse chimera. Results: Bcl-XL was strongly expressed in RL-251 but not in H-295 and neither expressed the Bcl-2 protein. G and D induced greater dose-dependent inhibition of cell proliferation in RL-251 than in H-295 cells and completely suppressed growth of tumors with high expression of Bcl-XL (p<0.05) while there was no growth suppression in tumors without Bcl-XL expression. Conclusion: This study provided proof of concept that expression of Bcl-XL determines response to proapoptosis drugs. Profiling adrenal tumors for expression of anti-apoptosis genes may provide clues to their potential response to drugs that induce apoptosis.