Novel Approach using shRNA of IQGAP1 for Colon Cancer Therapy: HCT116 as a Surrogate Model Colorectal Carcinoma

Document Type : Research Articles


1 Cell Biology Department, Biotechnology Research Institute, National Research Centre, 33 Bohouth St., 12622, Dokki, Cairo, Egypt.

2 Pharmacognosy Department, National Research Centre, El-Behooth St., 12622 Dokki, Cairo, Egypt.

3 Pharmaceutical Industries, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

4 Department of Biochemistry and Molecular Biology, College of Pharmacy, Al-Azhar University, Nasr City, Cairo, Egypt.

5 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Sinai University, 41636 Kantara Branch, Egypt.

6 Department of Pharmacology and Toxicology, College of Pharmacy, Al-Azhar University, Cairo, Egypt.

7 Protein Research Department, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications, Alexandria, Egypt.

8 Hormones Department, Medicine and Clinical Studies Research Institute, National Research Centre, Cairo, 12622 Egypt.


Background: Colorectal carcinoma (CRC) represents life-threatening problems worldwide. IQ motif containing GTPase activating protein 1 (IQGAP1) is acting as oncogenesis regulators. RNAi is proposed as promising cancer therapeutics. Objective: The objective of this work to explore the consequences of the IQGAP1 silence as a goal for treating CRC using the HCT166 cells as a model for human colon cancer. Methods: RNAi technology was used to design a short specific sequence of RNA (shRNA) to silence the IQGAP1 oncogene. The impact of IQGAP1 silencing on IQGAPs, Ras, IL-8, and TRAIL was investigated. Furthermore, the effect of IQGAP1 silencing on cell viability, proliferation, apoptosis, and invasive capacity was investigated. Results: The present results revealed that IQGAP1 shRNA-treated HCT166 cells showed no invasive capacity compared to the control cells. The silencing of IQGAP1 induced remarkable downregulation of IQGAP1, RAS (H&K), IL-8, CXCR1, CXCR2, NF-kB, BCL-2, and apoptosis of HCT166 cells. On the contrary, IQGAP2, IQGAP3, DR4, DR5, CASP-3, and BAX genes were significantly up-regulated. Conclusion: The IQGAP1 regulates the expression of IQGAPs, Ras, IL-8 receptors, and the apoptotic network. Therefore, the silence of IQGAP1 is a promising strategy for colon cancer therapy.


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