Expression of Anti-apoptosis Genes Determines the Response of Adrenal Cancer to Apoptosis-inducing Chemotherapy

• Published in: Anticancer research 2010-12, Vol.30 (12), p.4805-4809
• Main Authors: SCHTEINGART, David E, BENITEZ, Ricardo, BRADFORD, Carol, NARAYAN, Ajita, SHAOMENG WANG
• Format: Article
• Language: English
• Subjects: Adrenal Cortex Neoplasms - drug therapy; Adrenal Cortex Neoplasms - genetics; Adrenal Cortex Neoplasms - metabolism; Adrenal Cortex Neoplasms - pathology; Adrenals. Adrenal axis. Renin-angiotensin system (diseases); Animals; Apoptosis - drug effects; Apoptosis - genetics; bcl-X Protein - biosynthesis; bcl-X Protein - genetics; Biological and medical sciences; Cell Line, Tumor; Endocrinopathies; Genes, bcl-2; Gossypol - pharmacology; Humans; Malignant tumors; Medical sciences; Mice; Mice, SCID; Proto-Oncogene Proteins c-bcl-2 - biosynthesis; Proto-Oncogene Proteins c-bcl-2 - genetics; Taxoids - pharmacology; Tumors
• ISSN: 0250-7005; 1791-7530

This study tested the hypothesis that response of adrenal cortical carcinoma (ACC) to pro-apoptosis drugs depends on expression of anti-apoptosis genes. 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. 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