Human Papilloma Virus 16 E6 RNA Interference Enhances Cisplatin and Death Receptor-Mediated Apoptosis in Human Cervical Carcinoma Cells

• Published in: Molecular pharmacology 2012-05, Vol.81 (5), p.701-709
• Main Authors: Tan, Shinta, Hougardy, Brigitte M.T., Meersma, Gert J., Schaap, Bessel, de Vries, Elisabeth G.E., van der Zee, Ate G.J., de Jong, Steven
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Caspase 3 - metabolism; Caspase 8 - metabolism; Cisplatin - pharmacology; Cyclin-Dependent Kinase Inhibitor p21 - physiology; Female; HeLa Cells; Human papillomavirus 16; Humans; Oncogene Proteins, Viral - genetics; Oncogene Proteins, Viral - physiology; Receptors, Death Domain - physiology; Repressor Proteins - genetics; Repressor Proteins - physiology; RNA Interference; TNF-Related Apoptosis-Inducing Ligand - pharmacology; Tumor Suppressor Protein p53 - analysis; Uterine Cervical Neoplasms - drug therapy; Uterine Cervical Neoplasms - pathology; X-Linked Inhibitor of Apoptosis Protein - physiology
• ISSN: 0026-895X; 1521-0111
• DOI: 10.1124/mol.111.076539

In cervical cancer, the p53 and retinoblastoma (pRb) tumor suppressor pathways are disrupted by the human papilloma virus (HPV) E6 and E7 oncoproteins, because E6 targets p53 and E7 targets pRb for rapid proteasome-mediated degradation. We have investigated whether E6 suppression with small interfering RNA (siRNA) restores p53 functionality and sensitizes the HPV16-positive cervical cancer cell line SiHa to apoptosis by cisplatin, irradiation, recombinant human tumor necrosis factor-related apoptosis-inducing ligand (rhTRAIL), or agonistic anti-Fas antibody. E6 siRNA resulted in decreased E6 mRNA levels and enhanced p53 and p21 expression, demonstrating the restoration of p53 functionality in SiHa cells, without inducing high levels of apoptosis (