PI3K inhibitor enhances the cytotoxic response to etoposide and cisplatin in a newly established neuroendocrine cervical carcinoma cell line
| Autor: | Shing-Jyh Chang, Hsin-Yueh Yeo, Kuo-Ming Chang, Tze-Chien Chen, Yung-Jen Chuang, Zih-Yin Lai, Ya-Tse Chen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Combination therapy Cell Survival Cell Uterine Cervical Neoplasms Antineoplastic Agents Apoptosis PI3K inhibitor Pharmacology combination therapy 03 medical and health sciences Mice 0302 clinical medicine neuroendocrine cervical carcinoma Cell Line Tumor medicine Animals Humans Etoposide genotoxic drug Cell Proliferation Phosphoinositide-3 Kinase Inhibitors Cisplatin Cervical cancer business.industry Cell growth Papillomavirus Infections Drug Synergism BEZ235 medicine.disease Xenograft Model Antitumor Assays Carcinoma Neuroendocrine Disease Models Animal 030104 developmental biology medicine.anatomical_structure Oncology Cell culture 030220 oncology & carcinogenesis Cancer research Female business Biomarkers medicine.drug Research Paper DNA Damage |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Zih-Yin Lai 1 , Hsin-Yueh Yeo 1 , Ya-Tse Chen 1 , Kuo-Ming Chang 2 , Tze-Chien Chen 3 , Yung-Jen Chuang 1 and Shing-Jyh Chang 4 1 Department of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 30013, Taiwan (R.O.C.) 2 Department of Pathology, Hsinchu MacKay Memorial Hospital, Hsinchu 30071, Taiwan (R.O.C.) 3 Department of Obstetrics and Gynecology, MacKay Memorial Hospital, Taipei 10449, Taiwan (R.O.C.) 4 Department of Obstetrics and Gynecology, Hsinchu MacKay Memorial Hospital, Hsinchu 30071, Taiwan (R.O.C.) Correspondence to: Yung-Jen Chuang, email: yjchuang@life.nthu.edu.tw Shing-Jyh Chang, email: justine3@ms8.hinet.net Keywords: neuroendocrine cervical carcinoma, combination therapy, genotoxic drug, PI3K inhibitor, BEZ235 Received: February 14, 2017 Accepted: April 12, 2017 Published: April 21, 2017 ABSTRACT Background: Neuroendocrine 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. Results: The 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 Methods: A 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. Conclusions: The 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. |
| Databáze: | OpenAIRE |
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