Borik asit ve tamoksifen aynı anda uygulanmasının hormon reseptörü pozitif MCF-7 meme kanseri hücre dizilerinde sinerjistik etkisinin araştırılması
Küçük Resim Yok
Dosyalar
Tarih
2021
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Ege Üniversitesi, Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Giriş ve Amaç:
Kanser global olarak temel sağlık sorunu olmaya devam etmektedir. Meme kanseri dünya da ve ülkemizde kadınlarda en sık saptanan kanserdir. Meme kanseri tedavisinde cerrahi tedavi, kemoterapi, radyoterapi, hormonoterapi ve hedefe yönelik tedavi kullanılmaktadır. Özellikle hormon reseptörü pozitif olan hastalarda tamoksifen de dahil olmak üzere endokrin tedaviler kullanılmaktadır. Tamoksifen meme kanserinde hem cerrahi sonrası adjuvan tedavide hem de metastatik hastalıkta kullanılmaktadır. Tamoksifen kullanan hastalarda endişe verici durumlardan birisi tamoksifene karşı direnç gelişmesidir ve bu durum tedavide başarısızlığa yol açmaktadır. Bu yüzden literatürde tamoksifenin yeni türevleri ve kombinasyon çalışmaları bulunmaktadır. Tamoksifen preparat olarak tamoksifen sitrat formunda bulunmaktadır. Sitrat antioksidan özelliği ve aktif maddenin stabilitesini korumasından dolayı farmasötik preparatlarda sık kullanılan bir yardımcı maddedir. Borik asitin sitrat gibi zayıf bir asit olmasının yanında sitotoksik etkileride bulunmaktadır.Bu çalışmada tamoksifen ve borik asit kombinasyonlarının hormon reseptörü pozitif MCF-7 hücre dizilerinde hücresel canlılığa olan etkisi araştırılmaktadır.
Gereç ve Yöntem
Çalışmamızda östrojen reseptör pozitif hücre dizileri olan MCF-7 hücreleri kullanıldı. Tamoksifen ve borik asidin doz, zaman bağımlı ve kombine bir şekilde hücrelere uygulanması sonucu hücre canlılığında meydana gelen değişimler MTT (3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) analizi ile belirlendi. Tamoksifen ve borik asidin kombine uygulanmasıyla oluşan kombinasyon indeks değerleri Compusyn 1.0 programı kullanılarak hesaplandı. Elde edilen veriler GraphPad Prism 8.4 istatistik programı kullanılarak analiz edildi.
Bulgular:
Tamoksifen ve borik asidin MCF-7 hücre dizilerinde hücre canlılığına olan etkisini belirlemek amacıyla doz ve zaman bağımlı olarak Tamoksifen ve borik asid uygulaması gerçekleştirildi. Tamoksifenin 24. Saatte 25 μM, 48. Saatte 15 μM ve 72. Saatte 5 μM dan itibaren hücre canlılığını istatistiksel olarak azalttığı görüldü (p<0.05). Tamoksifenin MCF-7 hücre dizilerindeki hücre proliferasyonu için IC50 değerleri 24, 48 ve 72. saatler için sırasıyla 27.98 μM, 21.63 μM ve 18.22 μM olarak hesaplandı. Borik asitin 24. Ve 48. Saatlerde 5 mM, 72. Saatte ise 10mM dan itibaren hücre canlılığını istatistiksel olarak azalttığı görüldü (p<0.05). Borik asidin MCF-7 hücre dizilerindeki hücre proliferasyonu için IC50 değerleri 24, 48 ve 72. saatler için sırasıyla 65.93 mM, 30.25mM, 25.40mM olarak hesaplandı. Tamoksifen ve borik asitin birlikte kombine olarak uygulanması sonucu elde edilen tüm kombinasyon indeks değerlerinin 0.9 ila 1.1 değerleri arasında olduğu belirlendi. Tamoksifen ve borik asit kombine uygulamasının MCf-7 hücre dizilerinde additif etki gösterdiği görüldü.
Sonuç:
Yapmış olduğumuz çalışma ile tamoksifen ve borik asidin MCF-7 hücre dizilerinde doz ve zaman bağımlı olarak hücre canlılığını azalttığı, tamoksifen ve borik asit kombine uygulamasının ise hücre canlılığına additif olarak etki ettiği gösterilmiştir.
Introduction: Cancer continues to be the main health problem globally. Breast cancer is the most common cancer detected in women in the world and in our country. Surgical treatment, chemotherapy, radiotherapy, hormonal therapy and targeted therapy are used in breast cancer treatment. Endocrine treatments, including tamoxifen, are used, especially in patients with hormone receptor positive. Tamoxifen is used in both postoperative adjuvant therapy and metastatic disease in breast cancer. One of the worrying situations in patients using tamoxifen is the development of resistance to tamoxifen, which leads to treatment failure. Therefore, there are new derivatives and combination studies of tamoxifen in the literature. Tamoxifen is available in the form of tamoxifen citrate as a preparation. Citrate is used as an excipient in pharmaceutical preparations due to its antioxidant properties. It maintains stability of active ingredients and is used as a preservative. Besides being a weak acid like citrate, boric acid has cytotoxic effects. In this study, the effect of tamoxifen and boric acid combinations on cellular survival in hormone receptor positive MCF-7 cell lines is investigated. Materials and Methods Estrogen receptor positive cell lines, MCF-7 cells, were used in our study. Changes in cell viability as a result of dose, time dependent and combined application of tamoxifen and boric acid to cells were determined by MTT (3- (4,5-Dimethyl-2-thiazolyl) -2,5-diphenyl-2H-tetrazolium bromide) analysis. Combination index values obtained by the combined application of tamoxifen and boric acid were calculated using the Compusyn 1.0 program. The data obtained were analyzed using the GraphPad Prism 8.4 statistical program. Results In order to determine the effect of tamoxifen and boric acid on cell viability in MCF-7 cell lines, Tamoxifen and boric acid were administered in a dose and time dependent manner. It was observed that tamoxifen statistically decreased cell viability starting from 25 μM at 24th hour, 15 μM at 48th hour and 5 μM at 72nd hour (p<0.05).IC50 values of tamoxifen for cell proliferation in MCF-7 cell lines were calculated as 27.98 μM, 21.63 μM and 18.22 μM for 24, 48 and 72 hours, respectively. It was observed that boric acid decreased the cell viability statistically from 5 mM at 24th and 48th hours and 10mM at 72nd hour (p<0.05).IC50 values of boric acid for cell proliferation in MCF-7 cell lines were calculated as 65.93 mM, 30.25mM, 25.40mM for 24, 48 and 72 hours, respectively.It was determined that all combination index values obtained as a result of the combined application of tamoxifen and boric acid were between 0.9 and 1.1 values. It was observed that the combined application of tamoxifen and boric acid had an additive effect in MCf-7 cell lines. Conclusion In our study, it has been shown that tamoxifen and boric acid reduce cell viability in MCF-7 cell lines depending on dose and time, while the combined application of tamoxifen and boric acid has an additive effect on cell viability.
Introduction: Cancer continues to be the main health problem globally. Breast cancer is the most common cancer detected in women in the world and in our country. Surgical treatment, chemotherapy, radiotherapy, hormonal therapy and targeted therapy are used in breast cancer treatment. Endocrine treatments, including tamoxifen, are used, especially in patients with hormone receptor positive. Tamoxifen is used in both postoperative adjuvant therapy and metastatic disease in breast cancer. One of the worrying situations in patients using tamoxifen is the development of resistance to tamoxifen, which leads to treatment failure. Therefore, there are new derivatives and combination studies of tamoxifen in the literature. Tamoxifen is available in the form of tamoxifen citrate as a preparation. Citrate is used as an excipient in pharmaceutical preparations due to its antioxidant properties. It maintains stability of active ingredients and is used as a preservative. Besides being a weak acid like citrate, boric acid has cytotoxic effects. In this study, the effect of tamoxifen and boric acid combinations on cellular survival in hormone receptor positive MCF-7 cell lines is investigated. Materials and Methods Estrogen receptor positive cell lines, MCF-7 cells, were used in our study. Changes in cell viability as a result of dose, time dependent and combined application of tamoxifen and boric acid to cells were determined by MTT (3- (4,5-Dimethyl-2-thiazolyl) -2,5-diphenyl-2H-tetrazolium bromide) analysis. Combination index values obtained by the combined application of tamoxifen and boric acid were calculated using the Compusyn 1.0 program. The data obtained were analyzed using the GraphPad Prism 8.4 statistical program. Results In order to determine the effect of tamoxifen and boric acid on cell viability in MCF-7 cell lines, Tamoxifen and boric acid were administered in a dose and time dependent manner. It was observed that tamoxifen statistically decreased cell viability starting from 25 μM at 24th hour, 15 μM at 48th hour and 5 μM at 72nd hour (p<0.05).IC50 values of tamoxifen for cell proliferation in MCF-7 cell lines were calculated as 27.98 μM, 21.63 μM and 18.22 μM for 24, 48 and 72 hours, respectively. It was observed that boric acid decreased the cell viability statistically from 5 mM at 24th and 48th hours and 10mM at 72nd hour (p<0.05).IC50 values of boric acid for cell proliferation in MCF-7 cell lines were calculated as 65.93 mM, 30.25mM, 25.40mM for 24, 48 and 72 hours, respectively.It was determined that all combination index values obtained as a result of the combined application of tamoxifen and boric acid were between 0.9 and 1.1 values. It was observed that the combined application of tamoxifen and boric acid had an additive effect in MCf-7 cell lines. Conclusion In our study, it has been shown that tamoxifen and boric acid reduce cell viability in MCF-7 cell lines depending on dose and time, while the combined application of tamoxifen and boric acid has an additive effect on cell viability.
Açıklama
Anahtar Kelimeler
Tamoksifen, Borik Asit, Meme Kanseri, Tamoxifen, Boric Acid, Breast Cancer
