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• 基础研究 • 上一篇    下一篇

去氢表雄酮及其代谢产物对人肿瘤细胞系的抗增殖作用

姜艳芳1,赵平伟2,谭 岩1,方艳秋1,松崎静司3   

  1. (1.吉林大学第一医院中心实验室,吉林 长春 130021; 2.吉林大学第四医院肝胆外科,吉林 长春 130011;3.日本筑波大学消化内科,日本 筑波 305-8575)
  • 收稿日期:2008-05-08 修回日期:1900-01-01 出版日期:2008-11-28 发布日期:2008-11-28
  • 通讯作者: 谭 岩

Anti-proliferative effect of dehydroepiandrosterone and its metabolites on human tumor lines

JIANG Yan-fang1,ZHAO Ping-wei2,TAN Yan1,FANG Yan-qiu1,YASUSHI Matsuzaki3   

  1. (1.Central Laboratory,First Hospital,Jilin University,Changchun 130021,China; 2.Department of Hepatobiliary Surgery,Fouth Hospital,Jilin University,Changchun 130011,China; 3. Department of Gastroenterology and Hepatology,Institute of Clinical Medicine, Tsukuba University,Tsukuba,Ibaraki 305-8575,Japan)
  • Received:2008-05-08 Revised:1900-01-01 Online:2008-11-28 Published:2008-11-28
  • Contact: TAN Yan

摘要: 目的: 研究去氢表雄酮(DHEA)及其代谢物去氢表雄酮硫酸酯(DHEAs)对HepG2和HT-29细胞增殖的抑制作用及其机制。方法: HepG2和HT-29细胞分别分为对照组、不同浓度(1、 10、 50、 100及200 μmol•L-1)DHEA组和DHEAs组,孵育8、24、48及72 h后,分别采用噻唑蓝(MTT)比色法和BrdU 测定法检测DHEA对肿瘤细胞的生长抑制率,同时测定3-羟基-3-甲基戊二酸单酰A还原酶(HMGR)、葡萄糖-6-磷酸脱氢酶(G6PD)及乳酸脱氢酶(LDH)活性。结果: ①MTT法结果显示,与对照组比较,不同浓度DHEA组HepG2和HT-29细胞增殖抑制率均显著增加(P<0.05)。作用24 h时,100 μmol•L-1DHEA组细胞增殖抑制率降低最显著(P<0.05),而DHEAs组差异无显著性(P>0.05)。②BrdU法结果显示,当DHEA浓度在50、100和200 μmol•L-1时细胞的生长均显著受到抑制,尤其以HepG2细胞的生长抑制率最高(P<0.05)。③DHEA对HepG2细胞HMGR活性抑制率为62%,对HT-29细胞HMGR活性抑制率为51%,而 DHEAs则无明显作用。④100 μmol•L-1DHEA抑制G6PD的效力为85%,而DHEAs的抑制效力仅为6%。⑤DHEA和DHEAs对细胞LDH的活性影响组间比较差异无显著性(P>0.05)。结论:DHEA对HepG2和HT-29两种肿瘤细胞系均具有较强的抗增殖作用,能明显降低细胞的G6PD或HMGR活性,DHEAs则无明显作用。

关键词: 葡萄糖-6-磷酸脱氢酶, 3-羟基-3-甲基戊二酸单酰A还原酶

Abstract: To study the inhibitory effects of dehydroepiandrosterone (DHEA) and its metabolites-dehydroepiandrosterone sulfate (DHEAs) on the proliferation of HepG2 and HT-29 and their mechanism.Methods HepG2 and HT-29 were incubated by DHEA or DHEAs with different concentrations (1,10,50,100 and 200 μmol•L-1) for 8,24,48,72 h and routine culture was used as control.The inhibitory rate was detected by using MTT chromometry and BrdU assay respectively.The activities of 3-hydroxy-3-methylglutaryl coenzyme A reductase(HMGR),glucose -6-phosphate dehydrogenase (G6PD) and lactate dehydrogenase (LDH) were examined simultaneously. Results ①MTT chromometry:DHEA with different concentrations obviously inhibited the growth of HepG2 and HT-29 cells compared with control group(P<0.05).With the concentration of 100 μmol•L-1 and incubated for 24 h,the inhibitory effect of DHEA decreased markedly(P<0.05),whereas there was no significant difference of inhibitory effect between DHEAs group and control group (P>0.05).②BrdU assay:the growth of cells were significantly inhibited by DHEA with concentrations of 50,100 and 200 μmol•L-1,especially to HepG2 cells(P<0.05).③To HepG2 cells,HMGR activity could be inhibited by DHEA,and its inhibitory rate was 62%,while the inhibitory rate on HT-29 cells was 51%,however,DHEAs had no significant effect.④The inhibitory rate on G6PD activity was 85% by DHEA with the concentration of 100 μmol•L-1,whereas the inhibitory rate by DHEAs was about 6%.⑤DHEA and DHEAs had no significant effect on LDH activity(P>0.05). Conclusion DHEA has strong anti-proliferative effects on both HepG2 and HT-29 cell lines and inhibitory effects on the activities of G6PD or HMGR,however,DHEAs has no obvious effect.

Key words: glucose-6-phosphate dehydrogenase, 3-hydroxy-3-methyglutaryl coenzyme A reductase