Abstract
BackgroundNeuroendocrine cervical carcinoma (NECC) is a rare and aggressive subtype of cervical cancer. To date, no NECC cell-based model is available, which hinders the development of new therapeutic strategies for NECC. In this study, we derived a new NECC cell line from an ex vivo biopsy and used it to explore novel drug combination approach for NECC.ResultsThe stable HM-1 cell line displayed high expression levels of the neuroendocrine marker, synaptophysin. HM-1 cell transplantation could induce tumor growth in nude mice. As expected, the combination of etoposide and cisplatin synergistically inhibited HM-1 cell proliferation. Strikingly, when etoposide and cisplatin were combined with PI3K inhibitor BEZ235, the growth of HM-1 cells was significantly reduced. Taken together, the data implied the combination of etoposide and cisplatin with BEZ235 not only inhibited HM-1 cell proliferation but also increased cell apoptosis.Materials and MethodsA NECC tissue sample from a 75-year-old female patient was processed to derive a primary cell line annotated as HM-1. The features of HM-1 were analyzed to establish its characteristic profile. Next, HM-1 was treated with PI3K inhibitors, BKM120 and/or BEZ235, in combination with two well-known genotoxic drugs, etoposide and/or cisplatin, to evaluate which combination could serve as a more effective treatment approach. Their inhibiting effects on HM-1 were evaluated by cell viability, apoptosis, and target kinase expression.ConclusionsThe newly established NECC cell line HM-1 could serve as a cell-based model for NECC research. The synergistic drug combination of PI3K inhibitor with genotoxic drugs might become a potential new treatment strategy against NECC.
Highlights
Cervical cancer is one of the leading gynecological cancers contributing to female death worldwide
When etoposide and cisplatin were combined with PI3K inhibitor BEZ235, the growth of HM-1 cells was significantly reduced
The data implied the combination of etoposide and cisplatin with BEZ235 inhibited HM-1 cell proliferation and increased cell apoptosis
Summary
Cervical cancer is one of the leading gynecological cancers contributing to female death worldwide. A recent study has reported 528, 000 new cases of cervical cancer and 266, 000 deaths in 2012 [1]. The most common types of cervical cancer are squamous cell carcinoma (70%) and adenocarcinoma (25%) [2]. The neuroendocrine cervical carcinoma (NECC) is a rare subtype of cervical cancer, and accounts for only approximately 2% of all cervical malignancies [3]. The 5-year survival rate for NECC (35.7%) is much lower than www.impactjournals.com/oncotarget squamous cell carcinoma (60.5%) and adenocarcinoma (69.7%) combined [4]. Neuroendocrine cervical carcinoma (NECC) is a rare and aggressive subtype of cervical cancer.
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