[Expression of Notch intracellular domain in cervical cancer and effect of DAPT on cervical cancer cell].
OBJECTIVE
To study the expression and clinical significance of Notch intracellular domain (NICD) in cervical cancer and the effects of N-[N-(3,5-difluorophenyl)acetyl-L-alanyl]-S-phenyl glycine t-butyl ester (DAPT), a gamma-secretase inhibitor on the proliferation and apoptosis of cervical cancer cell lines.


METHODS
Western blot was used to detect the expression of NICD in the tissues of 40 cervical cancers and 21 normal cervix and its relationship with clinical features of cervical cancer was also analyzed. Proliferation of SiHa and HeLa cervical cells was determined by methyl thiazolyl tetrazolium (MTT) assay, cell cycles and apoptosis and index of proliferation were detected by flow cytometry method. The expression of NICD in SiHa and HeLa cells incubated with DAPT was detected by western blot.


RESULTS
The expression level of NICD in cervical cancers was significantly higher than that of normal cervical tissues (1.237 +/- 0.353 vs 0.938 +/- 0.105, P < 0.05). The NICD expression was higher in cervical cancers with high grade, lymph node involvement and parametrial invasion than that with low-middle grade (1.496 +/- 0.540 vs 1.150 +/- 0.216), without lymph node involvement (1.419 +/- 0.532 vs 1.159 +/- 0.210) and no parametrial invasion (1.718 +/- 0.710 vs 1.183 +/- 0.258), respectively (all P < 0.05). The expression of NICD in cervical adenocarcinoma was higher than that of squamous cell cancer (1.463 +/- 0.395 vs 1.162 +/- 0.187, P < 0.05). After SiHa and HeLa cells were incubated with DAPT, NICD expression was significantly lower than that in control (P < 0.05). The effects of DAPT inhibited the proliferation and prompted the apoptosis of SiHa and HeLa cells was depended on its concentrations and times.


CONCLUSIONS
NICD may play a key role in the occurrence and progress of cervical cancer. The mechanism of DAPT inhibited the proliferation and prompted the apoptosis of SiHa and HeLa cells may be due to decreased the formation of NICD.
Sun
Xiao-mei
XM
Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing 100034, China.
Wen
Hong-wu
HW
Chen
Chun-ling
CL
Liao
Qin-ping
QP
D000328:Adult; D000368:Aged; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004151:Dipeptides / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D051880:Receptors, Notch / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
D000970:Antineoplastic Agents; D004151:Dipeptides; C419410:N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester; D051880:Receptors, Notch; D053829:Amyloid Precursor Protein Secretases