Evaluation of the effect of anti-SOX۹ specific siRNA on the sensitivity of colon cancer cells to doxorubicin

Introduction: Colon cancer is one of the leading causes of cancer-related death in the western world. SOX۹ transcription factor, which is overexpressed in many cancers, plays a role in various cellular processes such as tumor progression, metastasis and drug resistance. Silencing of gene expression by siRNA is one of the most powerful tools to suppress the expression of specific genes. In this study, the effect of anti-SOX۹-specific siRNA on the growth, apoptosis and susceptibility of doxorubicin-resistant SW۴۸ cells was evaluated. Methods: The relative expression of β-actin, SOX۹, S۱۰۰P, P۵۳, P۲۱, MDM۲, Bax, PUMA and Survivin genes were measured using RT-PCR technique followed by treatment with SOX۹ and doxorubicin siRNA. The effect of SOX۹ and doxorubicin siRNA alone and in combination on tumor cell growth and survival were evaluated using cell proliferation and MTT assays, respectively. Cell apoptosis was also evaluated using ELISA cell death assay. Results: The results of our study showed that SOX۹ siRNA significantly decreased the expression of SOX۹, S۱۰۰P, P۵۳, Survivin and MDM۲ genes and increased the expression of P۲۱, Bax and PUMA genes. Doxorubicin treatment increased the expression of P۵۳, P۲۱, Bax and PUMA genes and decreased the expression of MDM۲ and Survivin genes. Treatment of cancer cells with each drug decreased cell growth and survival compared to the control group, and the rate of cell apoptosis was increased by drug treatment. On the other hand, the combination of drugs showed a greater effect of single treatment on cell growth, survival and apoptosis. Conclusion: The results of our studies indicated that overexpression of SOX۹ plays an important role in chemotherapy resistance in colorectal cancer. Therefore, it is possible that SOX۹ may be a new therapeutic target for the treatment of patients with this disease.

Keywords:

doxorubicin , colon cancer , small interfering RNA , SOX۹