Down-regulation of Sonic hedgehog signaling pathway activity is involved in 5-fluorouracil-induced apoptosis and motility inhibition in Hep3B cells - PubMed (original) (raw)
Affiliations
- PMID: 18776995
Free article
Down-regulation of Sonic hedgehog signaling pathway activity is involved in 5-fluorouracil-induced apoptosis and motility inhibition in Hep3B cells
Qiyu Wang et al. Acta Biochim Biophys Sin (Shanghai). 2008 Sep.
Free article
Abstract
The Sonic hedgehog (SHh) pathway plays a critical role in normal embryogenesis and carcinogenesis, but its function in cancer cells treated with 5-fluorouracil (5-FU) remains unknown. We examined the expression of a subset of SHh signaling pathway genes, including SHh, SMO, PTC1, Su(Fu) and HIP in human hepatocellular carcinoma (HCC) cell lines, Hep3B and HepG2, treated with 5-FU by reverse transcription-polymerase chain reaction. Using trypan blue analysis, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling assay, we also detected the apoptosis of Hep3B cells resulting from the transfection of pCS2-Gli1 expression vector combined with 5-FU treatment. The motility of the cells was detected by scratch wound closure assay. The expression and subcellular location of PTC1 protein in Hep3B cells treated by 5-FU were also investigated by Western blot analysis and immunofluorescent microscopy. The results indicated that the expression of SHh pathway target molecules at both messenger RNA and protein levels are evidently down-regulated in Hep3B cells treated with 5-FU. The overexpression of Gli1 restores cell viability and, to some extent, the migration abilities inhibited by 5-FU. Furthermore, 5-FU treatment affects the subcellular localization of PTC1 protein, a key member in SHh signaling pathway. Our data showed that the down-regulation of SHh signaling pathway activity was involved in 5-FU-induced apoptosis and the inhibition of motility in hedgehog-activated HCC cell lines. This implies that the combination of SHh signaling pathway inhibitor and 5-FU-based chemotherapy might represent a more promising strategy against HCC.
Similar articles
- Partial contribution of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/TRAIL receptor pathway to antitumor effects of interferon-alpha/5-fluorouracil against Hepatocellular Carcinoma.
Yamamoto T, Nagano H, Sakon M, Wada H, Eguchi H, Kondo M, Damdinsuren B, Ota H, Nakamura M, Wada H, Marubashi S, Miyamoto A, Dono K, Umeshita K, Nakamori S, Yagita H, Monden M. Yamamoto T, et al. Clin Cancer Res. 2004 Dec 1;10(23):7884-95. doi: 10.1158/1078-0432.CCR-04-0794. Clin Cancer Res. 2004. PMID: 15585621 - Expression of sonic hedgehog signaling components in hepatocellular carcinoma and cyclopamine-induced apoptosis through Bcl-2 downregulation in vitro.
Chen XL, Cheng QY, She MR, Wang Q, Huang XH, Cao LQ, Fu XH, Chen JS. Chen XL, et al. Arch Med Res. 2010 Jul;41(5):315-23. doi: 10.1016/j.arcmed.2010.06.003. Arch Med Res. 2010. PMID: 20851287 - Characterization of cell death events induced by anti-neoplastic drugs cisplatin, paclitaxel and 5-fluorouracil on human hepatoma cell lines: Possible mechanisms of cell resistance.
Brenes O, Arce F, Gätjens-Boniche O, Díaz C. Brenes O, et al. Biomed Pharmacother. 2007 Jul;61(6):347-55. doi: 10.1016/j.biopha.2007.02.007. Epub 2007 Mar 9. Biomed Pharmacother. 2007. PMID: 17399942 - Hedgehog signaling pathway and gastrointestinal stem cell signaling network (review).
Katoh Y, Katoh M. Katoh Y, et al. Int J Mol Med. 2006 Dec;18(6):1019-23. Int J Mol Med. 2006. PMID: 17089004 Review. - The sonic hedgehog signaling network in development and neoplasia.
Chari NS, McDonnell TJ. Chari NS, et al. Adv Anat Pathol. 2007 Sep;14(5):344-52. doi: 10.1097/PAP.0b013e3180ca8a1d. Adv Anat Pathol. 2007. PMID: 17717435 Review.
Cited by
- Topical 5-fluorouracil application in management of odontogenic keratocysts.
Akhter Lone P, Ahmed Wani N, Ahmed Janbaz Z, Bibi M, Kour A. Akhter Lone P, et al. J Oral Biol Craniofac Res. 2020 Oct-Dec;10(4):404-406. doi: 10.1016/j.jobcr.2020.07.008. Epub 2020 Jul 22. J Oral Biol Craniofac Res. 2020. PMID: 32775182 Free PMC article. - Targeting Smoothened as a New Frontier in the Functional Recovery of Central Nervous System Demyelinating Pathologies.
Del Giovane A, Ragnini-Wilson A. Del Giovane A, et al. Int J Mol Sci. 2018 Nov 20;19(11):3677. doi: 10.3390/ijms19113677. Int J Mol Sci. 2018. PMID: 30463396 Free PMC article. Review. - MiR-145 is upregulated in the retarded preimplantation embryos and modulates cholesterol levels in mice preimplantation embryos through targeting Abca1.
Jian O, MengXia N, Shiyu X, QingXia M, QinYan Z, Jie D, Wei W, Jiaojiao W, Hong L, Yining H. Jian O, et al. Reprod Biol Endocrinol. 2022 Dec 12;20(1):168. doi: 10.1186/s12958-022-01044-8. Reprod Biol Endocrinol. 2022. PMID: 36510317 Free PMC article. - Cancer stem cells in hepatocellular carcinomas.
Das P, Gupta SD. Das P, et al. Indian J Med Res. 2015 Oct;142(4):362-5. doi: 10.4103/0971-5916.169191. Indian J Med Res. 2015. PMID: 26609026 Free PMC article. No abstract available. - Liver cancer stem cells.
Mikhail S, He AR. Mikhail S, et al. Int J Hepatol. 2011;2011:486954. doi: 10.4061/2011/486954. Epub 2011 Jun 30. Int J Hepatol. 2011. PMID: 21994859 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Miscellaneous