Investigation of the effects of specific chemotherapeutics and cholesterol drugs on an in vitro brain tumor model

Althouhg brain tumors are less common in adults compared to other tumors, they are one of the most common causes of cancer-related morbidity and mortality in the infants and children. One of the biggest problems about brain tumors is that chemotherapy drugs cannot reach the brain in the desired dose due to the blood-brain barrier. Chemotherapy drugs are given in combination with other drugs to increase treatment efficiency. On the other hand; Cholesterol is a steroid substance that forms an important component of the animal cell membrane. The loss of cholesterol feedback inhibition mechanisms that regulate cholesterol synthesis is an important feature of malignant transformation. From the literature review, a reasonable assumption is that tumor growth inhibition can be achieved by restricting the presence of cholesterol or cholesterol synthesis. Recently, it was found that simvastatin and lovastatin, which are cholesterol-regulating drugs, and the effects of simultaneous administration of chemotherapeutics (gemcitabine and carmustine) on in vitro brain tumor model were not investigated. In the current thesis, ıt ıs aimed to fill this gap in the literature. Cell Viability Detection Kit-8 was used to determine the effects of test compounds on cell viability and IC20 concentrations were determined for each compound in human neuroblastoma SH-SY5Y cells. Then, the effects of test compounds on apoptosis were revealed both colorimetrically and by western blot analysis. According to the results obtained, statins inhibited proliferation in a dose-dependent manner, both when administered alone and with chemotherapeutics. In particular, it was demonstrated in both methods that lovastatin induced apoptosis by increasing the efficiency of both gemcitabine and carmustine. As a result of the findings from the tests, ıt is suggested that statins may be a new neuroblastoma treatment option that could potentially enhance the effectiveness of currently used anticancer drugs.