期刊文献+

3,3’-二吲哚甲烷对宫颈癌SiHa细胞增殖抑制的实验研究 被引量:4

Experimental study of 3,3'-diindolylmethane on inhibiting proliferation of human cervical cancer SiHa cell line
下载PDF
导出
摘要 目的研究吲哚-3-甲醇(I3C)的重要衍生物3,3’-二吲哚甲烷(DIM)对宫颈癌SiHa细胞增殖和凋亡的影响。方法采用CCK-8法检测不同浓度DIM对SiHa细胞体外生长的抑制作用,流式细胞术检测DIM对SiHa细胞凋亡的影响,荧光显微镜观察细胞形态的变化;Western blotting检测不同浓度DIM对SiHa细胞凋亡相关蛋白表达的影响。结果 DIM对SiHa细胞的抑制作用呈时间-剂量依赖性,DIM对SiHa细胞干预48h的半数抑制浓度(IC50)为44.44μmol/L。分别以25、50、100μmol/L的DIM处理48h后,SiHa细胞的凋亡率分别为(10.09±1.32)%、(21.11±3.36)%和(55.46±6.33)%,阴性对照组为(4.56±0.52)%,组间差异有统计学意义(P<0.05)。不同浓度DIM处理48h后,荧光显微镜下SiHa细胞呈现皱缩、变圆,并形成明显的凋亡小体。Western blotting显示随着DIM浓度的增加,SiHa细胞中MAPK家族的ERK、p38和p-p38蛋白的表达水平受抑制,JNK、p-JNK蛋白的表达水平上调,PI3K家族的Akt、p-Akt、PI3K p110α、PI3K p110β、PI3K classⅢ、GSK3-β、p-PDK1和p-c-Raf蛋白的表达也受到抑制。结论 DIM能抑制SiHa细胞的生长并诱导细胞凋亡,其作用机制是通过对MAPK家族和PI3K家族凋亡相关蛋白表达的调控实现的,并将有可能成为一种有效的抗宫颈癌药物。 Objective To investigate the potential anti-proliferative and pro-apoptotic effects of 3,3-diindolylmethane( DIM), important derivatives of Indo-3-carbinol ( I3 C) on SiHa cells. Methods Cell proliferation was detected by cell counting Kit-8 and cell apoptosis was analyzed by flow cytometry. Morphological changes accompanying cell apoptosis were observed with fluorescence micro- scope after Hoeehst 33258 staining. In addition, changes of proteins expression involved in MPAK and PI3K pathway were determined by Western blotting. Results DIM treatment inhibited the proliferations and induced the apoptosis of SiHa cells significantly in a time- and dose-dependent manner. After DIM treatment for 48h,the calculated IC50 of DIM for SiHa cells was 44.44μmoL/L. The apoptotic ratio in SiHa cells were (4. 56 ± 0. 52 )% , ( 10. 09± 1.32)% , (21. 11±3.36) % and (55.46 ±6. 33 ) % at 0, 25, 50 and 100μmol/L DIM. Evident morphological changes including membrane shrinking, round shaping and budding to form apoptotic bodies were observed in SiHa cells after DIM treatment for 48h at different concentration. In addition, expressions of ERK, p-ERK, p38 and p-p38, which were involved in MAPK pathway, were down-regulated when the dose of DIM increased. Another proteins involved in MAPK pathway, such as JNK and p-JNK were up-regulated. Furthermore, DIM treatment significantly suppressed the expressions of Akt, p-Akt, PI3K pll0α, PI3K pll0β, PI3K class m, GSK3-β, p-PDK1 and p-e-Raf which were involved in PI3K pathway. Conclusion These re- sults demonstrated that DIM exerted anti-tumor effects on SiHa cells through its anti-proliferative and pro-apoptotic roles. The molecular mechanisnl for these effects may be related to its regulatory effects on MAPK and PI3K pathway and apoptosis proteins. DIM might be a preventive and therapeutic agent against cervical cancer.
出处 《临床肿瘤学杂志》 CAS 2012年第9期775-779,共5页 Chinese Clinical Oncology
关键词 3 3’-二吲哚甲烷 宫颈癌 SIHA细胞 增殖 凋亡 3, 3 ' -Diindolyhnethane Cervical cancer SiHa cells Proliferation Apoptosis
  • 相关文献

参考文献30

  • 1World Health Organization. Globocan 2008, cervical cancer incidence, mortality and prevalence worldwide in 2008:IRAC [ EB/ OL]. [ 2012 - 03 - 15 ]. http ://globocan. iarc. fr/.
  • 2Newall AT, Beutels P, Wood JG, et al. Cost-effectiveness analyses of human papillomavirus vaccination[J]. Lancet Infect Dis, 2007,7 (4) :289 - 296.
  • 3Tanaka T, Bai T, Yukawa K, et al. Optimal combination chemotherapy and chemoradiotherapy with etoposide for advanced cervical squamous cancer cells in vitro[ J]. Oncol Rep, 2006,15 (4) :939 -947.
  • 4Sarkar FH, Li Y, Wang Z, et al. Cellular signaling perturbation by natural products [ J ]. Cell Signal, 2009, 21 ( 11 ) : 1541 - 1547.
  • 5Brew CT, Aronchik I, Hsu JC, et al. Indole-3-carbinol activates the ATM signaling pathway independent of DNA damage to stabilize p53 and induce G1 arrest of human mammary epithelial cells[J]. IntJCancer, 2006,118(4):857-868.
  • 6Rahman KM, Aranha O, Glazyrin A,et al. Translocation of Bax to mitochondria induces apoptotic cell death in indole-3-carbinol (I3C) treated breast cancer cells [ J ]. Oncogene, 2000, 19 (50) :5764-5771.
  • 7Chang X, Tou JC, Hong C, et al. 3,3' -Diindolylmethane inhibits angiogenesis and the growth of transplantable human breast carcinoma in athymic mice[ J ]. Carcinogenesis, 2005,26 (4) : 771 - 778.
  • 8Safe S, Papincni S, Chintharlapalli S. Cancer chemotherapy with indole-3-carhinol, bis(3 '-indolyl)methane and synthetic analogs [ J ]. Cancer Lett ,2008,269 (2) :326 - 338.
  • 9Khwaja FS, Wynne S, Posey I, et al. 3,3' -diindolylmethane induction of p75NTR-dependent cell death via the p38 mitogen-activated protein kinase pathway in prostate cancer cells [ J ]. Cancer Prey Res ( Phiia), 2009,2 ( 6 ) : 566 - 571.
  • 10Chinnakannu K, Chen D, Li Y, et al. Cell cycle-dependent effects of 3,3 ' -diindolylmethane on proliferation and apoptosis of prostate cancer cells[J]. J Cell Physiol, 2009,219( 1 ) :94 - 99.

同被引文献50

  • 1余畅,邓华瑜.JAK抑制剂AG490诱导乳腺癌细胞凋亡及对Survivin表达的影响[J].癌症,2006,25(10):1227-1231. 被引量:6
  • 2KIM H W, KIM J, LEE S, et al. 3, 3 '- Diindolylmethane inhibits lipopolysaccharide-induced microglial hyperactivation and attenuates brain inflammation [ J]. Toxicol Sci,2013.
  • 3STEINMETZ K A, POTTER J D. Vegetables, fruit, and cancer prevention: a review [ J]. J Am Diet Assoc, 1996, 96 : 1027-1039.
  • 4AGGARWALB B, SHISHODIA S. Molecular targets of dietary agents for prevention and therapy of cancer [ J]. Biochem Pharmacol,2006, 71 : 1397-1421.
  • 5VIVAR O I, LIN C L, FIRESTONE G L, et al. 3, 3 ' -Diindolylmethane induces a G( 1 ) arrest in human prostate cancer cells irrespective of androgen receptor and p53 status [J]. Biochem Pharmacol,2009, 78: 469-476.
  • 6AGGARWAL B B, ICHIKAWA H. Molecular targets and anticaneer potential of indole-3-carbinol and its derivatives [J]. Cell Cycle,2005, 4: 1201-1215.
  • 7LI Y, KONG D, AHMAD A, et al. Antioxidant function of isoflavone and 3,3 '-diindolylmethane: are they important for cancer prevention and therapy.'? [J]. Antioxid Redox Signal,2013, 19: 139-150.
  • 8WATTENBERG L W, LOUB W D. Inhibition of polyeyclic aromatic hydrocarbon-induced neoplasia by naturally occurring indoles [ J]. Cancer Res, 1978, 38: 1410-1413.
  • 9ABDELRAHIM M, NEWMAN K, VANDERLAAG K, et al. 3, 3 '-diindolylmethane (DIM) and its derivatives induce apoptosis in pancreatic cancer cells through endoplasmic reticulum stress-dependent upregulation of DR5 [ J]. Carcinogenesis,2006, 27 : 717-728.
  • 10STRESSER D M, BJELDANES L F, BAILEY G S, et al. The anticarcinogen 3,3 ' -diindolylmethane is an inhibitor of cytochrome P-450 [ J]. J Biochem Toxieol,1995, 10: 191-201.

引证文献4

二级引证文献5

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部