[Effect of topotecan on expression of aquaporin protein 5 and nuclear factor-kappaB in ovarian cancer SKOV3 cells].
OBJECTIVE
Overexpression of aquaporin protein 5 (AQP5) is associated with the metastasis, migration and angiogenesis of ovarian cancer, but its function in cell proliferation has not been described. This study was to explore the effects of topotecan (TPT) on the expression of AQP5, nuclear factor-kappaB (NF-kappaB) and its receptor IkappaBalpha in ovarian cancer SKOV3 cells.


METHODS
When SKOV3 cells were treated with TPT of various concentrations for different time, cell proliferation was measured by MTT assay, the expression of AQP5, NF-kappaB and IkappaBalpha was detected by Western blot.


RESULTS
After SKOV3 cells were incubated with 0.4 microg/mL TPT for 24 h, the expression of AQP5, NF-kappaB p65 in cytoplasm and nuclei, and IkappaBalpha in cytoplasm were decreased, and remained at low levels till 72 h (P<0.05). When SKOV3 cells were treated with 0.2, 0.4, 0.6 and 0.8 microg/mL TPT for 24 h, the expression of AQP5 as well as NF-kappaB p65 and IkappaBalpha in nuclei were decreased (P<0.005). The protein level of AQP5 was decreased by 57.9% when cells were treated with 0.8 microg/mL TPT. AQP5 expression was negatively correlated to the proliferation inhibition rate of SKOV3 cells induced by TPT (r=-0.965, P<0.05), and positively correlated to NF-kappaB p65 and IkappaBalpha expression (r=0.903, 0.896, P<0.05).


CONCLUSIONS
When inhibiting the proliferation of ovarian cancer cells, TPT may down-regulate the expression of AQP5 and NF-kappaB.
Chen
Xue-Jun
XJ
Department of Gynecology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310006, P.R. China.
Yang
Jian-Hua
JH
Zheng
Wei
W
D000970:Antineoplastic Agents / Q000494:pharmacology; D051402:Aquaporin 5 / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D003593:Cytoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D059004:Topoisomerase I Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D019772:Topotecan / Q000008:administration & dosage / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000378:metabolism*
C496036:AQP5 protein, human; D000970:Antineoplastic Agents; D051402:Aquaporin 5; D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; D059004:Topoisomerase I Inhibitors; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; D019772:Topotecan