PMID- 22781074
OWN - NLM
STAT- MEDLINE
DCOM- 20130215
LR  - 20131121
IS  - 0529-567X (Print)
IS  - 0529-567X (Linking)
VI  - 47
IP  - 3
DP  - 2012 Mar
TI  - [Impact of calcium channel antagonists for estrogen action on the endometrial 
      carcinoma HEC-1A cells].
PG  - 212-7
AB  - OBJECTIVE: To study the effects of nifedipine and mibefradil on the cell 
      proliferation, apoptosis, migration on the HEC-1A in vitro and also study the 
      mRNA and protein expression levels of the calcium channel alpha1D (Cav1.3) and 
      calcium channel alpha1G (Cav3.1) to discuss the effects of the calcium 
      antagonists on the mechanisms of the endometrial carcinoma. METHODS: (1) Add 10 
      micromol/L nifedipine and mibefradil at 15 minutes before adding 10 micromol/L 
      17beta-estradiol (17beta-E(2)) and 100 micromol/L b-estradiol-6-(O-carboxymethyl)oxime 
      (E(2)-BSA) to the HEC-1A in different time including 0, 5, 15, 30, 60, 120 
      minutes. Then the changes of mRNA and protein were detected by reverse 
      transcripiton (RT)-PCR and western-blot. (2) Add 1.25, 2.5, 5, 10, 20, 40, 80, 
      100 micromol/L nifedipine and mibefradil to the HEC-1A at 24, 48, 96 hours to detect 
      the cell proliferation by 3-(4,5)-dimethylthiahiazo 
      (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) method. (3) Add 10 micromol/L nifedipine 
      and mibefradil to the HEC-1A, then detect the apoptosis at 0 minute, 30 minutes, 
      1 hour, 6 hours, 24 hours and migration in vitro at 36 hours with transwell 
      methods. RESULTS: (1) After the pretreated effect of the nifedipine before 
      17beta-E(2), the mRNA express of Cav1.3 genes was lowest at 15 minutes, and returned 
      to the control level after 30 minutes. The protein level didn't change very much 
      in 30 minutes, but rose after 60 minutes. The Cav3.1 genes mRNA express was 
      lowest at 5 minutes, rose at 30 minutes and returned to the 0 minute level 
      gradually. (2) After the pretreated effect of the nifedipine before E(2)-BSA, the 
      Cav1.3 genes mRNA was lowest at 5 minutes and returned at 15 minutes. The protein 
      level rose gradually in 15 minutes but reduced after 15 minutes. The Cav3.1 mRNA 
      and protein level were reduced at every time point. (3) After the pretreated 
      effect of the mibefradil before 17beta-E(2), there was no change of mRNA expression 
      of Cav1.3 genes. The protein level rose at 15 and 60 minutes, there was no change 
      in any other time. The Cav3.1 genes mRNA were gradually reduced and the protein 
      level rose at 15 minutes, and there was no change in any other times. (4) After 
      the pretreated effect of the mibefradil before E(2)-BSA, the mRNA and protein of 
      Cav1.3 levels were reduced after 15 minutes. There was no mRNA expression of 
      Cav3.1, while the protein level was lowest at 15 minutes. (5) Nifedipine and 
      mibefradil affected HEC-1A proliferation depended on the different concentration 
      and interval time points. There was significant difference than those in control 
      group (P < 0.05). (6) There were statistical differences in apoptosis rate after 
      adding nifedipine (P < 0.05), while rose at mibefradil treated the same time (24 
      hours: 8.41 +/- 0.07, 0 minute: 3.74 +/- 0.18; P < 0.05). (7) The numbers of stained 
      cells after both nifedipine and mibefradil treated reduced more than control 
      group. CONCLUSIONS: (1) Nifedipine and mibefradil could inhibit both the effect 
      of the estrogen on the L-type and T-type calcium channel in short time, meanwhile 
      the mibefradil effects last long time. (2) The inhibited effect of the mibefradil 
      on the proliferation, apoptosis and migration of HEC-1A cells in vitro is more 
      significant than that by nifedidipine.
FAU - Bao, Xiao-xia
AU  - Bao XX
AD  - Department of Gynecology, Peking University People's Hospital, Beijing, China.
FAU - Wang, Jian-liu
AU  - Wang JL
FAU - Wei, Li-hui
AU  - Wei LH
LA  - chi
PT  - English Abstract
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Zhonghua Fu Chan Ke Za Zhi
JT  - Zhonghua fu chan ke za zhi
JID - 16210370R
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Calcium Channels, L-Type)
RN  - 0 (Calcium Channels, T-Type)
RN  - 0 (Estrogen Antagonists)
RN  - 0 (Estrogens)
RN  - 0 (RNA, Messenger)
RN  - 27B90X776A (Mibefradil)
RN  - 35048-47-6 (estradiol-6-(O-carboxymethyl)oxime)
RN  - 4TI98Z838E (Estradiol)
RN  - I9ZF7L6G2L (Nifedipine)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Calcium Channel Blockers/*pharmacology
MH  - Calcium Channels, L-Type/genetics/*metabolism
MH  - Calcium Channels, T-Type/genetics/*metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Endometrial Neoplasms/*metabolism/pathology
MH  - Estradiol/analogs & derivatives/pharmacology
MH  - Estrogen Antagonists/pharmacology
MH  - Estrogens/pharmacology
MH  - Female
MH  - Humans
MH  - Mibefradil/*pharmacology
MH  - Nifedipine/*pharmacology
MH  - RNA, Messenger/genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Time Factors
EDAT- 2012/07/12 06:00
MHDA- 2013/02/16 06:00
CRDT- 2012/07/12 06:00
PHST- 2012/07/12 06:00 [entrez]
PHST- 2012/07/12 06:00 [pubmed]
PHST- 2013/02/16 06:00 [medline]
PST - ppublish
SO  - Zhonghua Fu Chan Ke Za Zhi. 2012 Mar;47(3):212-7.