Triple negatif meme kanseri hücre hattında immün hücre eşliğinde pantoprazol ve paklitaksel kombinasyonunun etkisi
Date
2024-09-03
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Publisher
Bursa Uludağ Üniversitesi
Abstract
Meme kanseri kadınlarda en sık görülen kanser türüdür. Triple negatif meme kanseri (triple negative breast cancer, TNBC) agresif doğası gereği kemoterapiye direnç geliştirebilmektedir. Bunun altında yatan sebeplerden biri de tümör mikroçevre (tumor microenvironment, TME) asitliğidir. Bu engeli aşabilmek için V-ATPaz gibi asit salgılamada görevli pompaları inhibe eden proton pompası inhibitörleri (PPI) kullanılarak daha etkili bir tedavi seçeneği olabileceği düşünülmüştür. Bu tezde bir TNBC hücre hattı olan EMT6 ile splenosit (SPL) hücreleri ko-kültürüne, meme kanserinde en sık kullanılan kemoterapi ilaçlarından biri olan paklitaksel (PTX) ve bir PPI olan pantoprazol (PPZ) birlikte uygulanmıştır. Hücrelerin canlılığı 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) metodu ile değerlendirilmiştir. Çalışmamız sonucunda EMT6 hücreleri üzerine uygulanan PPZ’nin PTX’in toksik etkisini artırmadığı ancak SPL hücrelerine uygulandığında ise proliferasyonuna yol açtığı gözlenmiştir. Bunun yanısıra, PPZ ile PTX kombine olarak SPL’lere uygulandığında PPZ’nin, PTX’in SPL’ler üzerindeki toksisitesini azalttığı saptanmıştır.
Breast cancer is the most common type of cancer in women. Triple negative breast cancer (TNBC) can develop resistance to chemotherapy due to its aggressive nature. One of the underlying reasons for this is tumor microenvironment (TME) acidity. In order to overcome this obstacle, proton pump inhibitors (PPIs), which inhibit acid secretion pumps such as V-ATPase, were thought to be a more effective treatment option. In this thesis, paclitaxel (PTX), one of the most commonly used chemotherapy drugs in breast cancer, and pantoprazole (PPZ), a PPI, were applied to the co-culture of EMT6, a TNBC cell line, and splenocyte (SPL) cells. The viability of the cells was evaluated by the 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. As a result of our sturdy, it was observed that PPZ applied to EMT6 cells did not increase the toxic effect of PTX, but when applied to SPL cells, it caused proliferation. In addition, when PPZ and PTX were applied in combination to SPLs, it was determined that PPZ reduced the toxicity of PTX on SPLs.
Breast cancer is the most common type of cancer in women. Triple negative breast cancer (TNBC) can develop resistance to chemotherapy due to its aggressive nature. One of the underlying reasons for this is tumor microenvironment (TME) acidity. In order to overcome this obstacle, proton pump inhibitors (PPIs), which inhibit acid secretion pumps such as V-ATPase, were thought to be a more effective treatment option. In this thesis, paclitaxel (PTX), one of the most commonly used chemotherapy drugs in breast cancer, and pantoprazole (PPZ), a PPI, were applied to the co-culture of EMT6, a TNBC cell line, and splenocyte (SPL) cells. The viability of the cells was evaluated by the 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. As a result of our sturdy, it was observed that PPZ applied to EMT6 cells did not increase the toxic effect of PTX, but when applied to SPL cells, it caused proliferation. In addition, when PPZ and PTX were applied in combination to SPLs, it was determined that PPZ reduced the toxicity of PTX on SPLs.
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Keywords
Meme kanseri, Pantoprazol, Paklitaksel, T hücre, Tümör asiditesi, Breast cancer, Pantoprazole, Paclitaxel, T cell, Tumor acidity