Enhanced anticancer effect of cetuximab combined with stabilized silver ion solution in EGFR-positive lung cancer cells

Manguoğlu, Ayşe Esra; ÖZKAN, Ödül; ERDOĞAN, Ayse; Kiraz, Nadir; özkan, aysun

doi:10.1515/tjb-2018-0033

Enhanced anticancer effect of cetuximab combined with stabilized silver ion solution in EGFR-positive lung cancer cells

Ayşe ERDOĞAN, (Alanya Alaaddin Keykubat University, Faculty of Engineering, Genetic and Bioengineering Department, Alanya, Antalya)

Aysun ÖZKAN, (Akdeniz University, Science Faculty, Biology Department, Antalya, Turkey)

Ödül ÖZKAN, (Baskent University, Faculty of Medicine, Ankara, Turkey)

Esra MANGUOĞLU, (Akdeniz University, Medicine Faculty, Medical Biology and Genetics Department, Antalya, Turkey)

Nadir KİRAZ (Akdeniz University, Science Faculty, Chemistry Department, Antalya, Turkey)

Türk Biyokimya Dergisi

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Yıl: 2019 Cilt: 44 Sayı: 4 Sayfa Aralığı: 426 - 437 Metin Dili: İngilizce DOI: 10.1515/tjb-2018-0033 İndeks Tarihi: 05-06-2020

Enhanced anticancer effect of cetuximab combined with stabilized silver ion solution in EGFR-positive lung cancer cells

Öz:

Background: Cytotoxic, antiproliferative, cell cycle inhibi- tive, oxidative and apoptotic effects of cetuximab [anti- body for epidermal growth factor receptor (EGFR)] alone and together with stabilized silver ion solution (St-Ag) on P-H1299, R-H1299, A-431 and A-549 cells were investigated. Materials and methods: Cytotoxic effects of cetuximab alone and together with St-Ag on cells were determined by Cell Titer-Blue® Cell Viability and Lactate Dehydrogenase Activ- ity tests. Cell cycle distributions and apoptosis were detected by reverse transcription polymerase chain reaction (RT-PCR). Results: St-Ag enhanced cetuximab cytotoxic effect on all cells. LDH activity, as a result of cell death, was found the highest level at treatment of cetuximab with St-Ag in all cells. Both treatment increased caspase-3/7 activity which is apoptotic enzyme was found higher in A-549 cells than other cells. Also, treatment of cetuximab with St-Ag caused increasing Bax/Bcl-2 ratio in all cells. Cetuximab with St-Ag treatment increased glutathione peroxidase activity in all cells generating oxidative stress. Proliferating Cell Nuclear Antigen (PCNA), topoisomerase II-alpha (except R-H1299), cyclin D1 and D2 genes expression were decreased in all cells which explain the cell cycle inhibition effect.Conclusion: These findings suggest that treatment of cetuximab combined with St-Ag exhibit more carcinogen- esis reducing potential than cetuximab alone.

Anahtar Kelime:

EGFR-pozitif akciğer kanseri hücrelerinde cetuximab’ın stabilize gümüş iyon çözeltisiyle birlikte artmış antikanser etkisi

Öz:

Amaç: Cetuximab’ın (epidermal büyüme faktörü reseptörü antikoru) tek başına ve stabilize gümüş iyon çözeltisiyle (St-Ag) birlikte sitotoksik, antiproliferatif, hücre döngüsü engelleyici, oksidatif ve apoptotik etkileri P-H1299, R-H1299, A-431 ve A-549 hücrelerinde incelenmiştir. Gereç ve Yöntem: Cetuximab’ın tek başına ve St-Ag ile birlikte hücreler üzerindeki sitotoksik etkileri Cell Titer- Blue® Hücre Canlılık testi ve Laktat dehidrogenaz aktivite testleri ile belirlenmiştir. Hücre döngüsü dağılımları ve apoptoz ters transkriptaz polimeraz zincir reaksiyonu (Rt- PCR) ile belirlenmiştir. Bulgular: St-Ag, cetuximab’ın sitotoksik etkisini tüm hücrelerde arttırmıştır. Her iki uygulamanın apoptotik enzim olan kaspaz-3/7 aktivitesini A-549 hücrelerinde diğer hücrelere göre daha fazla arttırdığı bulunmuştur. Ayrıca, cetuximab’ın St-Ag ile birlikte uygulanması tüm hücrelerde Bax/Bcl-2 oranının artmasına neden olmuştur. Cetuximab’ın St-Ag ile birlikte uygulanması tüm hücre- lerde oksidatif stres yaratarak glutatyon peroksidaz akti- vitesini arttırmıştır. Hücre döngüsü inhibisyon etkisini açıklayan Prolifere Hücre Nükleer Antijeni (PCNA), topoi- zomeraz II-alfa (R-H1299 hariç), siklin D1 ve D2 genlerinin ekspresyonu tüm hücrelerde azalmıştır Sonuç: Bu bulgular, cetuximab’ın St-Ag ile birlikte uygu- lanmasının, tek başına cetuximab uygulamasından daha fazla karsinogenezisi azaltma potansiyelinin olduğunu göstermektedir.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

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APA	ERDOĞAN A, özkan a, ÖZKAN Ö, Manguoğlu A, Kiraz N (2019). Enhanced anticancer effect of cetuximab combined with stabilized silver ion solution in EGFR-positive lung cancer cells. , 426 - 437. 10.1515/tjb-2018-0033
Chicago	ERDOĞAN Ayse,özkan aysun,ÖZKAN Ödül,Manguoğlu Ayşe Esra,Kiraz Nadir Enhanced anticancer effect of cetuximab combined with stabilized silver ion solution in EGFR-positive lung cancer cells. (2019): 426 - 437. 10.1515/tjb-2018-0033
MLA	ERDOĞAN Ayse,özkan aysun,ÖZKAN Ödül,Manguoğlu Ayşe Esra,Kiraz Nadir Enhanced anticancer effect of cetuximab combined with stabilized silver ion solution in EGFR-positive lung cancer cells. , 2019, ss.426 - 437. 10.1515/tjb-2018-0033
AMA	ERDOĞAN A,özkan a,ÖZKAN Ö,Manguoğlu A,Kiraz N Enhanced anticancer effect of cetuximab combined with stabilized silver ion solution in EGFR-positive lung cancer cells. . 2019; 426 - 437. 10.1515/tjb-2018-0033
Vancouver	ERDOĞAN A,özkan a,ÖZKAN Ö,Manguoğlu A,Kiraz N Enhanced anticancer effect of cetuximab combined with stabilized silver ion solution in EGFR-positive lung cancer cells. . 2019; 426 - 437. 10.1515/tjb-2018-0033
IEEE	ERDOĞAN A,özkan a,ÖZKAN Ö,Manguoğlu A,Kiraz N "Enhanced anticancer effect of cetuximab combined with stabilized silver ion solution in EGFR-positive lung cancer cells." , ss.426 - 437, 2019. 10.1515/tjb-2018-0033
ISNAD	ERDOĞAN, Ayse vd. "Enhanced anticancer effect of cetuximab combined with stabilized silver ion solution in EGFR-positive lung cancer cells". (2019), 426-437. https://doi.org/10.1515/tjb-2018-0033

APA	ERDOĞAN A, özkan a, ÖZKAN Ö, Manguoğlu A, Kiraz N (2019). Enhanced anticancer effect of cetuximab combined with stabilized silver ion solution in EGFR-positive lung cancer cells. Türk Biyokimya Dergisi, 44(4), 426 - 437. 10.1515/tjb-2018-0033
Chicago	ERDOĞAN Ayse,özkan aysun,ÖZKAN Ödül,Manguoğlu Ayşe Esra,Kiraz Nadir Enhanced anticancer effect of cetuximab combined with stabilized silver ion solution in EGFR-positive lung cancer cells. Türk Biyokimya Dergisi 44, no.4 (2019): 426 - 437. 10.1515/tjb-2018-0033
MLA	ERDOĞAN Ayse,özkan aysun,ÖZKAN Ödül,Manguoğlu Ayşe Esra,Kiraz Nadir Enhanced anticancer effect of cetuximab combined with stabilized silver ion solution in EGFR-positive lung cancer cells. Türk Biyokimya Dergisi, vol.44, no.4, 2019, ss.426 - 437. 10.1515/tjb-2018-0033
AMA	ERDOĞAN A,özkan a,ÖZKAN Ö,Manguoğlu A,Kiraz N Enhanced anticancer effect of cetuximab combined with stabilized silver ion solution in EGFR-positive lung cancer cells. Türk Biyokimya Dergisi. 2019; 44(4): 426 - 437. 10.1515/tjb-2018-0033
Vancouver	ERDOĞAN A,özkan a,ÖZKAN Ö,Manguoğlu A,Kiraz N Enhanced anticancer effect of cetuximab combined with stabilized silver ion solution in EGFR-positive lung cancer cells. Türk Biyokimya Dergisi. 2019; 44(4): 426 - 437. 10.1515/tjb-2018-0033
IEEE	ERDOĞAN A,özkan a,ÖZKAN Ö,Manguoğlu A,Kiraz N "Enhanced anticancer effect of cetuximab combined with stabilized silver ion solution in EGFR-positive lung cancer cells." Türk Biyokimya Dergisi, 44, ss.426 - 437, 2019. 10.1515/tjb-2018-0033
ISNAD	ERDOĞAN, Ayse vd. "Enhanced anticancer effect of cetuximab combined with stabilized silver ion solution in EGFR-positive lung cancer cells". Türk Biyokimya Dergisi 44/4 (2019), 426-437. https://doi.org/10.1515/tjb-2018-0033