Association of XPO1 Overexpression with NF-κB and Ki67 in Colorectal Cancer

Document Type: Research Articles

Authors

1 Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok, Thailand.

2 Department of Pathology, Faculty of Medicine and Health Sciences, University of Sana’a, Sana’a, Yemen.

3 Clinical Molecular Pathology Laboratory, Department of Clinical Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Abstract

Objectives: Exportin 1(XPO1), a nuclear exporter protein, has been gaining recognition in cancer progression and treatment. This study aimed to evaluate the association between the overexpression of XPO1 with NF-κB, Ki67 and clinicopathological characteristics in colorectal cancer (CRC) tissue samples and to explore the anti-proliferative effect of KPT-330, as XPO1 inhibitor, in colorectal cancer cell line. Methods: Forty CRC tissue samples were analyzed by immunostaining for the expressions of XPO1, NF-κB and Ki67 and then the anti-proliferative effect of the KPT-330 was also evaluated in HT29 colorectal cancer cell line. Results: XPO1 overexpression was observed in 52.5% of CRC and significantly apparent with strong intensity in tumor cells compared to the normal adjacent epithelium (P<0.001). Regarding to the histopathological characteristics, the XPO1 overexpression significantly associated with advanced tumor stages (P=0.049) and has great tendency towards moderate/poorly differentiated tumors. Although the XPO1 overexpression was strongly associated with high Ki67 expression (P=0.001), only Ki67 expression showed significant association with tumor size (P=0.012). No significant association was detected between the XPO1 overexpression and NF-κB, while the NF-κB positive expression was significantly associated with lymph node metastasis and Ki67 expression at P=0.027 and P= 0.007, respectively. The in vitro experiments showed a great impact of KPT-330, as XPO1 inhibitor, to inhibit cancer growth in dose and time dependent manner and significantly diminished the colony formation (P<0.001) of HT29 cells- associated with the expression of Ki67 (P<0.001). Conclusion: XPO1 overexpression and NF-κB expression may serve as potential biomarker associated with CRC pathogenesis and proliferation, while the KPT-330 is effectively inhibited-colon cancer growth in vitro. Further studies considering the prognostication role of XPO1 overexpression in CRC are required.
 

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