Partial Phenotypic Reversion of HeLa Cells by Long-Term Interferon-α Treatment

Abstract

Human papiliomaviruses (HPV) are associated with malignant cervical neoplasia. Several HPV-related diseases have been shown to be sensitive to interferon (IFN) treatment. HeLa cells contain and express the HPV type 18 genome and were used as a model for the evaluation of the viral expression regulation and the effect on the malignant phenotype during IFN treatment. Cells were treated continuously with 200 IU/ml IFN-α2b or natural leukocyte INF-α for six passages (42 days). Some IFN-induced changes were observed: decrease of HPV-18 mRNA expression, changes of cell morphology, and reduction of clonogenicity in soft agar. Tumorigenicity in nude mice was not modified. Other targets of the IFN system were analyzed, and an increase of the 2′,5′-oligoadenyIate synthetase mRNA level and a down-regulation of type I IFN receptor were found. These results demonstrate that long-term IFN-α treatment induces a partial phenotypic reversion of HeLa cells to a more differentiated stage where down-regulation of HPV-18 expression could play a central role. It therefore confirms that the IFN-α treatment may be therapeutically useful in cervix cancer produced by HPV-18.