Enhancing sensitivity of chemoresistant ovarian cancer cells to TRAIL and FAS mediated apoptosis by radiation       
Yazarlar (1)
Prof. Dr. Ercan ÇAÇAN Tokat Gaziosmanpaşa Üniversitesi, Türkiye
Makale Türü Açık Erişim Özgün Makale
Makale Alt Türü Ulusal alan endekslerinde (TR Dizin, ULAKBİM) yayınlanan tam makale
Dergi Adı Turk Hijyen Ve Deneysel Biyoloji Dergisi
Dergi ISSN 0377-9777 Scopus Dergi
Dergi Tarandığı Indeksler TR DİZİN
Makale Dili İngilizce
Basım Tarihi 01-2017
Cilt No 74
Sayı 3
Sayfalar 185 / 192
DOI Numarası 10.5505/TurkHijyen.2017.12499
Özet
Objective: Death receptors initiate apoptotic signals following interaction with their cognate ligands. However, expressions of death receptors are often downregulated during ovarian cancer progression and it has been recently asserted that suppression of death receptors is associated with resistance to chemotherapeutic drugs in ovarian cancer cells. Radiotherapy is a common treatment modality for several cancer types and it has been reported that low-dose ionizing radiation modulates tumor microenvironment. The purpose of the present study is to determine if sub-lethal ionizing radiation will modulate the expression of common death receptors in chemoresistant ovarian cancer cells and to investigate if reversed expression of death receptors will enhance TRAIL or FAS ligand (FASL) mediated apoptosis. Methods: Flow cytometry analyses were performed to determine the effects of chemotherapeutic drug, cisplatin, on chemosensitive and chemoresistant ovarian cancer cells viability, cellular expressions of death receptors and TRAIL or FAS mediated apoptosis, following sub-lethal irradiation in drug resistant ovarian cancer cells. Results: The majority of chemoresistant A2780-AD cells remain viable following a high dose of cisplatin treatment, while the drug sensitive A2780 cells started to die following low dose drug exposure. The results have demonstrated that 2 Gy or 5 Gy ionizing radiation enhances expression of death receptors, FAS and DR4, in multi drug resistant A2780-AD ovarian cancer cells. The data further have confirmed that sub-lethal ionizing radiation increases FAS/TRAIL-mediated apoptosis of the chemoresistant ovarian tumor cells. Conclusion: This study has suggested that sublethal radiation treatment may simultaneously increase immunogenicity of tumor cells and the induction of antitumor immunity to chemoresistant ovarian cancer cells.
Anahtar Kelimeler
Chemoresistance | FAS | Ovarian cancer | Radiation | TRAIL