Association of XPO1 Overexpression with NF-κB and Ki67 in Colorectal Cancer.
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.<br />.
['Aladhraei|Mohammed|M|', 'Kassem Al-Thobhani|Abdulla|A|', 'Poungvarin|Naravat|N|', 'Suwannalert|Prasit|P|']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D017209:Apoptosis D014408:Biomarkers, Tumor D049109:Cell Proliferation D015179:Colorectal Neoplasms D005260:Female D005500:Follow-Up Studies D019073:HT29 Cells D006801:Humans D006834:Hydrazines D028884:Karyopherins D019394:Ki-67 Antigen D008207:Lymphatic Metastasis D008297:Male D008875:Middle Aged D016328:NF-kappa B D011379:Prognosis D018160:Receptors, Cytoplasmic and Nuclear D014230:Triazoles D055815:Young Adult
NF-κB Ki67 Colorectal cancer (CRC) KPT-330 Exportin 1 (XPO1)