Investigation of the role of programmed cell death 10 (PDCD10) protein in multidrug resistance

Urfalı Mamatoğlu, Çağrı
Drug resistance, a major obstacle in chemotherapy, is the sum of several cellular alterations including resistance to induction of apoptosis. Apoptosis is a well-regulated cell death mechanism which is controlled by several signaling pathways and a vast number of proteins. Alterations in the proteins involved in the apoptotic regulation have been associated with drug resistance in cancer. Programmed Cell Death 10 (PDCD10) protein is a novel apoptotic regulator that is recently linked to the modulation of cellular proliferation and apoptosis. However, the role of PDCD10 in drug resistance has not been established. In this study, it was aimed to reveal the role of PDCD10 in drug resistance in different cancer cell lines. Gene expression analyses showed that PDCD10 expression was cell- and anti-cancer agent-specific. PDCD10 expression was significantly downregulated in doxorubicin- and docetaxel-resistant MCF7 cells while 2-fold upregulated in doxorubicin-resistant HeLa cells. On the other hand, PDCD10 expression did not show any significant change in doxorubicin-resistant K562 cells, however, more than 2-fold downregulation was observed in imatinib-resistant K562 subline. siRNA-mediated downregulation of PDCD10 expression in parental MCF7 cells resulted in an increase in docetaxel and doxorubicin resistance in these cells. whereas it caused resensitization in doxorubicin-resistant HeLa cells. Similarly, PDCD10 overexpression in parental HeLa cells elevated the resistance to doxorubicin while it promoted chemosensitivity in doxorubicin-resistant MCF7 cells. The downregulation in PDCD10 expression resulted in lower caspase 3/7 activity in MCF7 cells as the cells acquired resistance to etoposide-induced apoptosis. Consequently, the levels of apoptosis-related genes, BCL-2, BAX, SURVIVIN and PUMA, were altered. The results suggest that PDCD10 has a possible dual role in cancer drug resistance, both promoting and preventing the induction of apoptosis under different cellular conditions. PDCD10 could be a novel target for reversal of drug resistance in cancer.


Danışık, Nurseda; Acar, Ahmet; Özen, Can; Department of Biotechnology (2022-10-31)
The development of drug resistance in tumor cells is one of the biggest problems currently in the clinic. As the pace of drug discovery slows and each new drug becomes increasingly expensive to bring to market, it is becoming clearer that better model systems and an understanding of drug resistance mechanisms are needed for second-line therapies. The overall aim of this project is to investigate the clonal evolution and drug resistance in colorectal cancer cell lines Caco-2 and HT-29 by using cellular barco...
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Activation of the Wnt signaling in some types of cancer and its relation with chemotherapy resistance is a very interesting issue that has been emphasized in recent years. Although, it is known that increase in the activity of beta-catenin is important in blast transformation and drug resistance, the underlying mechanisms are still unclear. In this study, changes in the expression levels of 186 genes that are thought to be important in drug resistance and Wnt signaling pathways were determined by using qPCR...
Evaluation of methylation profiles of an epidermal growth factor receptor gene in a head and neck squamous cell carcinoma patient group
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Upregulation of the epidermal growth factor receptor (EGFR) gene has shown an important impact on the development of head and neck cancers due to its important regulation role on multiple cell signaling pathways. The aim of this study was to investigate the methylation pattern of the promoter region of the EGFR gene between head and neck squamous cell carcinoma (HNSCC) patients and a control group. Forty-seven unrelated HNSCC patients, clinically diagnosed at the Department of Otorhinolaryngology, Dlşkapl Y...
Effect of cobalt-60 (gamma radiation) on multidrug-resistant multiple myeloma cell lines
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Emergence of resistance to chemotherapy and radiotherapy is a major obstacle for the successful treatment of MM (multiple myeloma). Prednisone, vincristine and melphalan are commonly used chemotherapeutic agents for the treatment of MM. In the current study, we examined the presence of possible cross-resistance between these drugs and gamma (gamma) radiation. Prednisone, vincristine and melphalan resistant RPMI-8226 and U-266 MM cells were generated by stepwise increasing concentrations of the drugs. The se...
Differential gene expression analysis related to extracellular matrix components in drug-resistant RPMI-8226 cell line
Mutlu, Pelin; Gündüz, Ufuk (Elsevier BV, 2012-4)
Drug resistance remains a major obstacle to the successful use of chemotherapeutic drugs for many types of cancers including multiple myeloma. It is becoming increasingly apparent that tumor microenvironment could provide a shelter to malignant plasma cells that allow their survival after initial drug exposure. This study demonstrates alterations in gene expression levels of several extracellular matrix (ECM) components in prednisone, vincristine and melphalan-resistant RPMI-8226 myeloma cells. Resistant RP...
Citation Formats
Ç. Urfalı Mamatoğlu, “Investigation of the role of programmed cell death 10 (PDCD10) protein in multidrug resistance,” Ph.D. - Doctoral Program, Middle East Technical University, 2018.