RESUMEN

Protease inhibitors (PIs) and reverse transcriptase drugs are important components of highly active antiretroviral therapy (HAART) for treating human acquired immunodeficiency syndrome (AIDS). Long-term clinical therapeutic efficacy and treatment compliance of these agents have been limited by undesirable adverse effects and their oncogenicity has been queried. This study investigated the effects of selected antiretroviral agents on the expression of key apoptotic regulatory genes; Bax and Bcl-2 in two cervical cell lines HCS-2 and NCE16IIA by real-time qPCR gene expression and immunocytochemistry. The anti-apoptotic effects of the PI-LPV/r were investigated by cell death detection ELISA and acridine orange staining. All the antiretroviral drugs and combinations tested had no effects on Bax and Bcl-2 gene expression and protein localisation in both cell lines. The protease inhibitors-LPV/r exhibited significant (P<0.05) inhibition of camptothecin-induced apoptosis in the cervical cancer HCS-2 cell line but not in the normal immortalised NCE16IIA cell line. This anti-apoptotic property of HIV protease inhibitors, although shown so far not to involve protein and RNA synthesis might promote the development of cancer.

Asunto(s)

Apoptosis/efectos de los fármacos , Inhibidores de la Proteasa del VIH/efectos adversos , Nucleósidos/química , Proteínas Proto-Oncogénicas c-bcl-2/genética , Inhibidores de la Transcriptasa Inversa/efectos adversos , Proteína X Asociada a bcl-2/genética , Línea Celular Transformada , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Transformación Celular Neoplásica/inducido químicamente , Ensayo de Inmunoadsorción Enzimática , Femenino , Expresión Génica/efectos de los fármacos , Inhibidores de la Proteasa del VIH/química , Humanos , Inhibidores de la Transcriptasa Inversa/química , Neoplasias del Cuello Uterino/inducido químicamente