Abstract
The clinical management and treatment of cervical cancer, one of the most commonly diagnosed cancers and a leading cause of cancer-related female death, remains a huge challenge for researchers and health professionals. Cervical cancer can be categorized into two major subtypes: common squamous cell carcinoma (SCC) and adenocarcinoma (AC). Although it is a relatively rare histological subtype of cervical cancer, there has been a steady increase in the incidences of AC. Therefore, new strategies to treat cervical cancer are urgently needed. In this study, the potential uses of IFNγ-based therapy for cervical cancer were evaluated using bioinformatics approaches. Gene expression profiling identified that cell cycle dysregulation was a major hallmark of cervical cancer including SCC and AC subtypes, and was associated with poor clinical outcomes for cervical cancer patients. In silico and in vitro experimental analyses demonstrated that IFNγ treatment could reverse the cervical cancer hallmark and induce cell cycle arrest and apoptosis. Furthermore, we demonstrated that apigenin could enhance the anticancer activity of IFNγ in a HeLa cervical AC cell line by targeting cyclin-dependent kinase 1. Taken together, the present study suggests the selective therapeutic potential of IFNγ alone or in combination with apigenin for managing cervical SCC and AC.
Highlights
Persistent infection of high-risk human papillomavirus (HPV) has been identified as the main etiological factor for cervical cancer [1]
HeLa and SiHa cell lines, which represent the two major histological types of human cervical cancer, were treated with various doses of IFNγ for 72 h, after which cell viability was examined by MTT assay (Figure 1A)
AC patients have a worse prognosis than patients with squamous cell carcinoma (SCC); more specific therapeutic strategy for different histological subtypes of cervical cancer are needed
Summary
Persistent infection of high-risk human papillomavirus (HPV) has been identified as the main etiological factor for cervical cancer [1]. HPV oncogenes E6 and E7 are involved in the transformation and immortalization of cervical cells, and are required for malignant progression [1]. The standard therapeutic strategy for treatment of cervical cancer involves a combination of surgery, chemotherapy or radiotherapy. Effective therapeutic treatments for patients with metastatic or recurrent cervical cancer after platinumbased chemotherapy are still lacking [3]. The adverse effects of current chemotherapy regimens remain a major concern. The develop-ment of alternative therapeutic drugs or combination treatments is urgently needed to improve patient survival and reduce morbidity rates associated with standard of care therapies
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