Shiva Kamran1, Ensiyeh Seyedrezazadeh1, Dariush Shanehbandi2, Milad Asadi2,3, Venus Zafari1, Najibeh Shekari4, Leila Namvar1, Habib Zarredar5. 1. Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Science, Tabriz, Iran. 2. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 3. Department of Basic Oncology, Institute of Health Sciences, Ege University, Izmir, Turkey. 4. Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 5. Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Science, Tabriz, Iran. Habib_Zarredar@yahoo.com.
Abstract
PURPOSE: Colorectal cancer (CRC) is one of the most prevalence malignancies in a different society with a high rate of death. The KRAS and p38α axes have critical roles in the development, migration, and growth of numerous tumors, such as colorectal malignancy. KRAS mutation acts as an oncogene in various cancers and is correlated with the poor prognosis in colorectal tumors. Also, p38α plays different roles and exhibits tissue-dependent activity. In some tissues act as an oncogene while in others act as a tumor suppressor. In this research, we try to understand the effect of the P38α and KRAS genes suppression by specific siRNAs on the SW480 cell line progression. METHODS: We evaluate the impact of the P38α and KRAS gene knockdown by special siRNA on the growth and development of the SW480 cell line. SW480 cell line was treated with KRAS and P38α siRNAs, and the cell viability, gene expression, migration ability, and rate of apoptosis were evaluated with MTT assay, real-time PCR, scratch test, and flow cytometry. RESULTS: After treatment of the cancer cell with KRAs and P38α siRNAs, cell viability reduced to 29.16%. Also, the expression levels of the KRAS and P38α genes reduced to 26.34% and 16.06%, respectively. Apoptosis rate after combination therapy with KRAS and P38α siRNAs increased to 72.1. Also, we found that these siRNAs suppress cell migration in SW480 cell lines. CONCLUSION: The current study showed that combination therapy with p38α and KRAS siRNA may be considered a novel therapy for colorectal tumor in future.
PURPOSE: Colorectal cancer (CRC) is one of the most prevalence malignancies in a different society with a high rate of death. The KRAS and p38α axes have critical roles in the development, migration, and growth of numerous tumors, such as colorectal malignancy. KRAS mutation acts as an oncogene in various cancers and is correlated with the poor prognosis in colorectal tumors. Also, p38α plays different roles and exhibits tissue-dependent activity. In some tissues act as an oncogene while in others act as a tumor suppressor. In this research, we try to understand the effect of the P38α and KRAS genes suppression by specific siRNAs on the SW480 cell line progression. METHODS: We evaluate the impact of the P38α and KRAS gene knockdown by special siRNA on the growth and development of the SW480 cell line. SW480 cell line was treated with KRAS and P38α siRNAs, and the cell viability, gene expression, migration ability, and rate of apoptosis were evaluated with MTT assay, real-time PCR, scratch test, and flow cytometry. RESULTS: After treatment of the cancer cell with KRAs and P38α siRNAs, cell viability reduced to 29.16%. Also, the expression levels of the KRAS and P38α genes reduced to 26.34% and 16.06%, respectively. Apoptosis rate after combination therapy with KRAS and P38α siRNAs increased to 72.1. Also, we found that these siRNAs suppress cell migration in SW480 cell lines. CONCLUSION: The current study showed that combination therapy with p38α and KRAS siRNA may be considered a novel therapy for colorectal tumor in future.
Authors: Shi Yu Yang; Anur Miah; Kevin M Sales; Barry Fuller; Alexander M Seifalian; Marc Winslet Journal: Int J Oncol Date: 2011-03-21 Impact factor: 5.650