Downregulated NM23-H1 expression is associated with intracranial invasion of nasopharyngeal carcinoma.
Because the focus of nasopharyngeal carcinoma (NPC) is very close to intracranial organs, it often makes incursions into cranial cavity. Identification of intracranial invasion-associated indicators will provide potential therapeutic targets for NPC patients with intracranial invasion. In this regard, Human Xpro HC-plus cancer-related gene chip was utilised to screen intracranial invasion-associated genes for NPC from the biopsied primary focus tissue samples. In all, 8 upregulated and 23 downregulated genes were obtained. VEGF165 and MMP-9, the two upregulated genes, and NM23-H1, the downregulated one, were further confirmed by immunohistochemistry, quantitative real-time PCR and western blot. Invasion-associated cellular and nude mouse models were subsequently employed to study the biological properties of NM23-H1. NM23-H1 expression was significantly lower in 5-8F cells compared with that in 6-10B cells. Moreover, patch-clamp and transwell chamber were adopted to investigate the invading potential-associated biological dynamic mechanisms in the two cell lines, and Ca(2+) current and motility were significantly elevated in 5-8F cells compared with that in 6-10B cells. Berberine, an inhibitor of Ca(2+) current, could substantially increase the expression of NM23-H1 and decrease 5-8F cell motility. The specificity of berberine on NM23-H1 and cell motility was confirmed by RNAi assay.
Liu
S J
SJ
Faculty of Integrative Medicine, Traditional Chinese Medicine University of Hunan, Changsha, People's Republic of China.
Sun
Y M
YM
Tian
D F
DF
He
Y C
YC
Zeng
L
L
He
Y
Y
Ling
C Q
CQ
Sun
S H
SH
D000328:Adult; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001599:Berberine / Q000494:pharmacology / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000517:prevention & control / Q000556:secondary*; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D054778:NM23 Nucleoside Diphosphate Kinases / Q000235:genetics*; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D054778:NM23 Nucleoside Diphosphate Kinases; D001599:Berberine; C517938:NME1 protein, human