Objective To investigate the effect of the ubiquitin-proteasome pathway inhibitor MG132 on the natural resistance to cisplatin in the human cervical cancer line (HCE1) muhicellular spheroid (HCE1/MCS) model and to probe it if MG132 could reverse the HCE1/MCS resistance to cisplatin, as well as the possible mechanism of drug resistance.Methods (1) HCE1/MCS was obtained using liquid overlay and rotating technique.(2)Four groups were established (MG132 group, cisplatin group, MG132 + cisplatin group, the control group).Cell viability were measured by trypan blue exclusion assay.Cell cycle and apoptosis were detected by flow cytometry.(3) The expression of nuclear factor (NF) kB of both HCE1 monolayer cells (HCEI/MC) and HCE1/MCS was detected by western blot, and the expression of B cell lymphoma/leukemia-2 (bcl-2) was detected by immunohistochemistry.Results (1) HCE1/MCS was established successfully.(2) Cell inhibited rate of HCE1/MC and HCE1/MCS was: in MG132 group, (11.67 ± 2.34) % vs (10.78 ± 1.17) % (P > 0.05) ; in MG132 + cisplatin group, (92.67 ± 2.52)% vs (91.33 ±2.18)% (P>0.05); in cisplatin group, (45.01±7.44)% vs (9.45±5.98)% (P<0.05).(3)The rate of apoptosis of HCE1/MC and HCE1/MCS were: in MG132 group, 8.14% and 5.97% ; in MG132 + cisplatin group, 99.01% and 95.22% ; in cisplatin group, 33.61% and 0.88%.(4)The expression level of NF-kB and the high expression rate of bcl-2 were: in HCE1/MCS of control group, 0.67 and 60% ; in HCE1/MCS of cisplatin group, 0.85 and 83% ; in HCE1/MCS of MG132 group, 0.39 and 20% ; in HCE1/MCS of MG132 + cisplatin group, 0.47 and 33%.Conclusions (1) HCE1/ MCS present natural resistance to cisplatin and may become a good model for the study of cervical cancer drug resistance in vitro.(2) MG132 could induce the inhibition and apoptosis of HCE1/MCS cells and partially reverse the natural resistance of HCE1/MCS to cisplatin, of which partially reverse the natural resistance may be in relation to the down-regulation of NF-kB and bcl-2 expression.

OBJECTIVE: To evaluate the clinical effect of letrozole (LE) alone on the ovulation induction in endometrial preparation for frozen-thawed embryo transfer (FET). METHODS: Totally 253 FET cycles were analyzed by case control study from October 2010 to June 2011. We divided ovulation disorders or menstrual disorders divided into 2 groups: a LE group on ovulation induction cycle (n=85), and a hormone replacement therapy (HRT) cycle group (n=84). Meanwhile those who ovulated normally were included in a natural cycle group (n=84). Demographics and clinical parameters of reproductive correlation of all patients were observed among these groups. RESULTS: The average clinical pregnancy rate of the LE group was higher than that of HRT cycle group (54.1% vs 44.04%; P<0.05). The difference in the parameters such as patients' demographics and other clinical indexs had no statistical significance (P>0.05). The estradiol level on human chorionic gonadotrophin (HCG) administration day in the natural cycle group [(341.19±113.14) pg/mL] was higher than that of the LE group [(279.70±127.80) pg/mL] (P<0.05). There was no significant difference in the number of maturation follicles and endometrial thickness on the HCG administration day between the LE group and the natural cycle group (P>0.05). CONCLUSION Ovulation induction with LE alone for endometrial preparation is superior to HRT cycle in FET and has similar clinical process and outcome to those of the natural cycle. It can be applied in endometrial preparation for FET effectively for those with anovulation or menstrual disorder.
Case-Control Studies ; Cryopreservation ; Embryo Transfer ; Endometrium ; drug effects ; physiology ; Female ; Fertility Agents, Female ; therapeutic use ; Fertilization in Vitro ; Humans ; Letrozole ; Nitriles ; therapeutic use ; Ovulation Induction ; methods ; Triazoles ; therapeutic use