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

使用IQGAP1 shRNA治疗结肠癌的新方法:HCT116作为结肠直肠癌的替代模型

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作者:Khairy M M A Zoheir, Khaled Mahmoud, Gamal I Harisa, Abdelkader Ashour, Hala E Abdel-Hamied, Amro A Amara, Karima F Mahrous, Ahmed A Abd-Rabou

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.

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.

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.

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.

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.

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