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Combination Therapy with KRAS and P38α siRNA Suppresses Colorectal Cancer Growth and Development in SW480 Cell Line

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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.

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Data Availability

Authors can confirm that all relevant data are included in the article or its supplementary information files.

Abbreviations

siRNA:

Small interfering RNA

KRAS:

Ki-ras2 Kirsten rat sarcoma virus

MTT:

3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide

EGFR:

Epidermal growth factor receptor

MAPK:

Mitogen activation protein kinase

NF-κB:

Nuclear factor kappa light chain enhancer of activated B cells

PP2AC:

Protein phosphatase 2 catalytic subunit alpha gene

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Funding

This study was supported by a grant from the Tuberculosis and Lung Disease Research Center, Tabriz University, of Medical Science, Tabriz, Iran.

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Authors and Affiliations

  1. Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Science, Tabriz, Iran

    Shiva Kamran, Ensiyeh Seyedrezazadeh, Venus Zafari, Leila Namvar & Habib Zarredar

  2. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Dariush Shanehbandi & Milad Asadi

  3. Department of Basic Oncology, Institute of Health Sciences, Ege University, Izmir, Turkey

    Milad Asadi

  4. Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Najibeh Shekari

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  1. Shiva Kamran
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  2. Ensiyeh Seyedrezazadeh
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  3. Dariush Shanehbandi
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  4. Milad Asadi
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Contributions

Conception and design of the research and the final version were done by Habib Zarredar and Ensiyeh Seyedrezazadeh. Shiva Kamran has done a lab test. Other authors participated in literature research, editing, conception, design figures, and discussion of the manuscript.

Corresponding author

Correspondence to Habib Zarredar.

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All experiment of this study has been done on SW480 cell line.

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Kamran, S., Seyedrezazadeh, E., Shanehbandi, D. et al. Combination Therapy with KRAS and P38α siRNA Suppresses Colorectal Cancer Growth and Development in SW480 Cell Line. J Gastrointest Canc 53, 597–604 (2022). https://doi.org/10.1007/s12029-021-00667-1

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