IκB kinase b Mediating the Downregulation of p53 and p21 by Lipopolysaccharide in Human Papillomavirus 16+Cervical Cancer Cells.
BACKGROUND
Cervical cancer is the second most common cancer of woman in the world, and human papillomavirus (HPV) infection plays an important role in the development of most of the cases. IκB kinase β (IKKβ) is a kinase-mediating nuclear factor kappa B (NF-κB) activation by phosphorylating the inhibitor of NF-κB (IκB) and is related by some diseases caused by virus infection. However, there is little known about the correlation between IKKβ and HPV infection in cervical cancer. This study aimed to investigate the expression of IKKβ protein in cervical cancer tissues and effects of inflammation on HPV positive or negative cervical cancer cells through detecting the expression of IKKβ, IκBα, p53, and p21 proteins after treated with lipopolysaccharide (LPS) to mimic bacterial infection. We also examined the effects of LPS on cervical cancer cells after blocking IKKβ with pharmacological inhibitor.


METHODS
Thirty-six matched specimens of cervical cancer and adjacent normal tissues were collected and analyzed in the study. The expression of IKKβ in the tissue specimens was determined by immunohistochemical staining. In addition, Western blot was used to detect the expression level changes of IKKβ, IκBα, p53, and p21 after LPS stimulated in the HPV16+ (SiHa) and HPV16- (C33A) cervical cancer cell lines. Furthermore, the effects of IKKβ inhibitor SC-514 on LPS-induced expression change of these proteins were investigated.


RESULTS
The expression of IKKβ was higher in cervical cancer than adjacent normal tissues, and there was no significant difference between tumor differentiation, size, and invasive depth with IKKβ expression. The LPS, which increased the expression level of IKKβ protein but decreased in the IκBα, p53 and p21 proteins, was illustrated in HPV16+ (SiHa) but not in HPV16- (C33A) cells. Moreover, IKKβ inhibitor SC-514 totally reversed the upregulation of IKKβ and downregulation of p53 and p21 by LPS in SiHa cells.


CONCLUSIONS
IKKβ may mediate the downregulation of p53 and p21 by LPS in HPV16+ cervical cancer cells.
Department of Gynecology, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China.
Zhi-Hui
ZH
Tan
Department of Gynecology, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China.
Yu
Y
Zhang
Department of Gynecology, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China.
Yan
Y
Tian
Department of Gynecology, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China.
Wei
W
Tan
Department of Gynecology, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China.
Ying-Hua
YH
Li
D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D052162:Human papillomavirus 16 / Q000472:pathogenicity*; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D013876:Thiophenes / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000821:virology*
D008070:Lipopolysaccharides; C477523:SC 514; D013876:Thiophenes; D016159:Tumor Suppressor Protein p53; D051550:I-kappa B Kinase; D016283:Proto-Oncogene Proteins p21(ras)