Document Type : Research Articles
Cell Biology Department, Biotechnology Research Institute, National Research Centre, 33 Bohouth St., 12622, Dokki, Cairo, Egypt.
Pharmacognosy Department, National Research Centre, El-Behooth St., 12622 Dokki, Cairo, Egypt.
Pharmaceutical Industries, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Department of Biochemistry and Molecular Biology, College of Pharmacy, Al-Azhar University, Nasr City, Cairo, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Sinai University, 41636 Kantara Branch, Egypt.
Department of Pharmacology and Toxicology, College of Pharmacy, Al-Azhar University, Cairo, Egypt.
Protein Research Department, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications, Alexandria, Egypt.
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.