Klorofilinin Meme Kanseri Kaynaklı Metastaz Üzerine Etkilerinin Araştırılması

Abstract

The development of drug resistance against chemotherapeutic agents is one of the main reasons for reducing the success of breast cancer treatment. It has been reported that the expression levels of Glutathione S-transferase P1, which belongs to the Glutathione S-transferase family of enzymes, increase in various cancer cell lines, and play a role in the development of drug resistance against chemotherapy. The antioxidant chlorophyllin is known to have an inhibitory effect on GSTP1. The other main factor that reduces the success of breast cancer treatment and leads mortality is distant tissue metastasis, especially in triple negative breast cancers. In this study, it is aimed to investigate the effect of chlorophyllin, an antioxidant and GSTP1 inhibitor, on triple negative breast cancer metastasis. For this purpose, the effect of the cancer drug docetaxel and/or chlorophyllin was investigated in vivo/in vitro in 4T1 breast cancer cell line and breast cancer animal model. For this purpose, the effects of both single and combined administration of chlorophyllin and docetaxel on cell viability, cell cycle and cell migration in 4T1 cell line were investigated. MMP-9 expression and total gelatinase activity were investigated in cell and tissue lysates. Total GST activity and glutathione levels were investigated in liver tissue lysates. Micrometastases were investigated in liver tissue sections. As a result, it was determined that the co-administration of chlorophyllin and docetaxel significantly inhibited cell migration in vitro (p<0.01). It was observed that the single application of chlorophyll significantly reduced the expression of MMP-9 in the tissues, and this effect was observed at higher levels when applied together with docetaxel (p<0.05). In the combined treatment group, a significant decrease was observed in the total gelatinase activity in vivo (p<0.01). It was determined that in vivo total glutathione (GSH) levels increased, and Glutathione S-transferase (GST) enzyme activity decreased in the chlorophyllin group (p<0.05). It was found that the micrometastatic lesions in the liver tissues were reduced in the combined treatment group. As a result of the study, it was concluded that the co-administration of chlorophyllin and docetaxel inhibited the migration step, which is one of the main processes in metastasis, and the invasion step, which is characterized by gelatinase enzyme expression/activity, and therefore may have a potential role in the control of metastatic processes.