title: Calcitriol Inhibits Cervical Cancer Cell Proliferation Through Downregulation of HCCR1 Expression.
abstract: Calcitriol (1α,25-dihydroxyvitamin D3) has demonstrated anticancer activity against several tumors. However, the underlying mechanism for this activity is not yet fully understood. Our experiment was designed and performed to address one aspect of this issue in cervical cancer. HeLa S3 cells were cultured in media with various concentrations of calcitriol. Cell proliferation and cell cycle were assessed by spectrophotometry and flow cytometry, respectively. The mRNA and protein expression levels of human cervical cancer oncogene (HCCR-1) and p21 were determined by RT-PCR and Western blot, respectively. Results indicated that calcitriol inhibited HeLa S3 cell proliferation and induced cell cycle arrest at the G1 phase. Calcitriol decreased HCCR-1 protein expression in a dose- and time-dependent manner. Furthermore, promoter activity analyses revealed that transcriptional regulation was involved in the inhibition of HCCR-1 expression. Overexpression of HCCR-1 in HeLa S3 cells reversed the inhibition of cell proliferation and G1 phase arrest that resulted from calcitriol treatment. In addition, calcitriol increased p21 expression and promoter activity. HCCR-1 overexpression decreased p21 expression and promoter activity. Thus, our results suggested that calcitriol inhibited HeLa S3 cell proliferation by decreasing HCCR-1 expression and increasing p21 expression.
authors.affiliation: Department of Oncology, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Lei
authors.forename: Xixia
authors.initials: X
authors.lastname: Zhao
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.forename: Kejun
authors.initials: K
authors.lastname: Nan
mesh_terms: D002117:Calcitriol / Q000494:pharmacology* / Q000627:therapeutic use; D015536:Down-Regulation / Q000187:drug effects* / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: C476732:LETMD1 protein, human; D011518:Proto-Oncogene Proteins; D002117:Calcitriol