Mide kanseri hücrelerinde Olea europaea yaprak özütünün tedavi edici potansiyelinin araştırılması
Date
2021-07-28
Authors
Tekin, Çağla
Journal Title
Journal ISSN
Volume Title
Publisher
Bursa Uludağ Üniversitesi
Abstract
Mide kanseri (Gastrik kanser; GK), dünya genelinde en yaygın görülen gastrointestinal sistem kanserlerinden biridir. İleri evre GK’nın mevcut tedavisi cerrahi rezeksiyon ve sonrasında uygulanan radyoterapi ve kemoterapi tedavisidir. İleri evre GK’ larda kemoterapi ilacı olarak genellikle 5-Fluorourasil (5-FU) ve sisplatin kullanılmaktadır. Ancak ileri evre GK hastalarında tümörün agresif oluşu ve hastaların ilaca direnç geliştirmesi sebebi ile tedavi olumsuz sonuçlanmaktadır. Günümüzde kanser tedavisinde kullanılmak üzere yeni stratejilerin geliştirilmesinde bitki özütlerinden yararlanılmakta ve çeşitli kanserlerde farklı kemoterapik ilaçlarla birlikte kombin tedavi yöntemlerine odaklanılmaktadır. Mevcut tez çalışmasında, Olea europea yaprak özütünün (OLE) tek başına ve kemoterapi ilacı olan 5-FU ve sisplatin ile kombin olarak kullanılmasıyla GK hücrelerinin canlılığı ve ölümü üzerine, tümör hücrelerinin agresifliğini baskılamasına, tümör büyüklüğü ve hücrelerde gelişen tedavi direncinin kırılması ve bu süreçlerde görev alan epigenetik mekanizmalar üzerine olası etkilerinin değerlendirilmesi amaçlanmaktadır. Bu amaç doğrultusunda OLE’nin ilaç direnci ile ilgili MDR genlerine, tümörün agresifliği ile ilişkili EMT ve CSC belirteçlerine ve epigenetik mekanizmalar ile ilişkili LncRNA’ların ekspresyon seviyelerine etkilerinin belirlenmesi için RT-PCR yöntemi kullanılmıştır. OLE’nin GK tümörlerinde hücre proliferasyonu WST, hücre ölümü Anneksin V analizleri ile, agresifliği, yara iyileşmesi, koloni oluşumu, tümörün büyüklüğü ve anjiogenez üzerine etkileri ise hücre kültür ortamında fonksiyonel analizler ile gerçekleştirilmiştir. Sonuç olarak, OLE’nin hücre proliferasyonunu azaltığı, hücreleri apoptotik yolla öldürdüğü ve kemoterapötikler ile birlikte EMT ve CSC belirteçlerini inhibe ederek tümörün agresifliğini baskıladığı, aynı zamanda MDR genlerinin ekspresyon seviyelerini düşürerek ilaç direncini önlediği tespit edilmiştir. Aynı zamanda OLE’nin tek başına ve kemoterapötikler ile birlikte tümör boyutunda küçülme gösterdiği ve anjiogenezi baskıladığı saptanmıştır.
Gastric cancer (Gastric cancer; GK) is one of the most common gastrointestinal system cancers worldwide. The current treatment of advanced stage GK is surgical resection followed by radiotherapy and chemotherapy treatment. 5-Fluorouracil (5-FU) and cisplatin are generally used as chemotherapy drugs in advanced GCs. However, in advanced stage GC patients, the treatment results in negative results due to the aggressiveness of the tumor and the development of drug resistance in the patients. Today, plant extracts are used in the development of new strategies for use in cancer treatment, and combined treatment methods with different chemotherapeutic drugs are focused on in various cancers. In the current thesis, it is aimed to evaluate the possible effects of Olea europea leaf extract (OLE) alone or in combination with the chemotherapy drug 5-FU and cisplatin on the viability and death, suppressing the aggressiveness of tumor cells, breaking the tumor size and treatment resistance developed in the cells and playing a role in these processes and evaluation of possible effects on epigenetic mechanisms of GK cells. For this purpose, RT-PCR method was used to determine the effects of OLE on MDR genes related to drug resistance, EMT and CSC markers associated with tumor aggressiveness, and expression levels of LncRNAs associated with epigenetic mechanisms. The effects of OLE on cell proliferation, WST, cell death, Annexin V analyzes in GK tumors, and the effects of OLE on wound healing, colony formation, tumor size and angiogenesis were performed by functional analyzes in cell culture. As a result, it has been determined that OLE reduces cell proliferation, kills cells apoptotically, suppresses tumor aggressiveness by inhibiting EMT and CSC markers together with chemotherapeutics, and also prevents drug resistance by reducing the expression levels of MDR genes. At the same time, it was determined that OLE alone and in combination with chemotherapeutics reduced tumor size and suppressed angiogenesis.
Gastric cancer (Gastric cancer; GK) is one of the most common gastrointestinal system cancers worldwide. The current treatment of advanced stage GK is surgical resection followed by radiotherapy and chemotherapy treatment. 5-Fluorouracil (5-FU) and cisplatin are generally used as chemotherapy drugs in advanced GCs. However, in advanced stage GC patients, the treatment results in negative results due to the aggressiveness of the tumor and the development of drug resistance in the patients. Today, plant extracts are used in the development of new strategies for use in cancer treatment, and combined treatment methods with different chemotherapeutic drugs are focused on in various cancers. In the current thesis, it is aimed to evaluate the possible effects of Olea europea leaf extract (OLE) alone or in combination with the chemotherapy drug 5-FU and cisplatin on the viability and death, suppressing the aggressiveness of tumor cells, breaking the tumor size and treatment resistance developed in the cells and playing a role in these processes and evaluation of possible effects on epigenetic mechanisms of GK cells. For this purpose, RT-PCR method was used to determine the effects of OLE on MDR genes related to drug resistance, EMT and CSC markers associated with tumor aggressiveness, and expression levels of LncRNAs associated with epigenetic mechanisms. The effects of OLE on cell proliferation, WST, cell death, Annexin V analyzes in GK tumors, and the effects of OLE on wound healing, colony formation, tumor size and angiogenesis were performed by functional analyzes in cell culture. As a result, it has been determined that OLE reduces cell proliferation, kills cells apoptotically, suppresses tumor aggressiveness by inhibiting EMT and CSC markers together with chemotherapeutics, and also prevents drug resistance by reducing the expression levels of MDR genes. At the same time, it was determined that OLE alone and in combination with chemotherapeutics reduced tumor size and suppressed angiogenesis.
Description
Keywords
Mide kanseri, Olea europaea yaprak özütü (OLE), Apoptoz, EMT, LncRNA, 3 boyutlu kültür, Gastric cancer, Olea europaea leaf extract (OLE), Apoptosis, 3D culture
Citation
Tekin, Ç. (2021). Mide kanseri hücrelerinde Olea europaea yaprak özütünün tedavi edici potansiyelinin araştırılması. Yayınlanmamış yüksek lisans tezi. Bursa Uludağ Üniversitesi Sağlık Bilimleri Enstitüsü.