Abstract
Numerous epidemiological studies suggest that sodium arsenite (SA) is a carcinogen. However, recent data have renewed the interest in its anti-carcinogenic properties. More than 90﹪of cervical cancer cells contain oncogenic human papillomaviruses (HPV). These cells usually possess wild-type p53 alleles, but its function is abrogated by HPV E6 oncoprotein through the ubiquitin pathway. Sodium arsenite had been shown to suppress HPV-16 E6 gene, induce p53 tumor suppressor pathway and enhanced apoptosis in E6-transfected lymphoblastoid cells. Additionally, E6-transfected TK6 cells were more sensitive to SA, but more resistant to IR than parental TK6 cells. In the present study, HPV-positive SiHa cervical cancer cells were treated with SA to examine p53 tumor suppressor pathway and apoptotic responses. After treatment with SA, it was found that SA could restore the expression of p53 and its downstream genes, p21 and mdm2, in SiHa cells in dose and time dependent manner. It was also shown that apoptosis occurred in SiHa cells through flow cytometric analysis, DNA fragmentation assay and apoptotic cells staining. In contrast to SA, X-irradiation could not restore p53 tumor suppressor pathway in SiHa cells. Pretreatment with SA could restore p53 function and enhance X-ray-induced cytotoxicity in SiHa cells. However, X-ray-induced cytotoxicity was not reduced by expression of a pCDNA3-p53m（containing mutated p53 at R273H） plasmid. Results from this study suggest that SA may serve as a radiosensitizer for X-ray therapeutic purpose in HPV-positive cancer cells. Therefore, further evidence is required to explore the relationship between SA-restored p53 expression and SA-enhanced radiosensitivity in SiHa cells.