Enhancement of SPHK1 in vitro by carbon ion irradiation in oral squamous cell carcinoma

Morihiro Higo, Katsuhiro Uzawa, Tetsuya Kawata, Yoshikuni Kato, Yukinao Kouzu, Nobuharu Yamamoto, Takahiko Shibahara, Jun etsu Mizoe, Hisao Ito, Hirohiko Tsujii, Hideki Tanzawa

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)


Purpose The purpose of this study was to assess the gene expression changes in oral squamous cell carcinoma (OSCC) cells after carbon ion irradiation. Methods and Materials Three OSCC cell lines (HSC2, Ca9-22, and HSC3) were irradiated with accelerated carbon ion beams or X-rays using three different doses. The cellular sensitivities were determined by clonogenic survival assay. To identify genes the expression of which is influenced by carbon ion irradiation in a dose-dependent manner, we performed Affymetrix GeneChip analysis with HG-U133 plus 2.0 arrays containing 54,675 probe sets. The identified genes were analyzed using the Ingenuity Pathway Analysis Tool to investigate the functional network and gene ontology. Changes in mRNA expression in the genes were assessed by real-time reverse transcriptase-polymerase chain reaction. Results We identified 98 genes with expression levels that were altered significantly at least twofold in each of the three carbon-irradiated OSCC cell lines at all dose points compared with nonirradiated control cells. Among these, SPHK1, the expression of which was significantly upregulated by carbon ion irradiation, was modulated little by X-rays. The function of SPHK1 related to cellular growth and proliferation had the highest p value (p = 9.25e-7 to 2.19e-2). Real-time reverse transcriptase-polymerase chain reaction analysis showed significantly elevated SPHK1 expression levels after carbon ion irradiation (p < 0.05), consistent with microarray data. Clonogenic survival assay indicated that carbon ion irradiation could induce cell death in Ca9-22 cells more effectively than X-rays. Conclusions Our findings suggest that SPHK1 helps to elucidate the molecular mechanisms and processes underlying the biologic response to carbon ion beams in OSCC.

Original languageEnglish
Pages (from-to)867-875
Number of pages9
JournalInternational Journal of Radiation Oncology Biology Physics
Issue number3
Publication statusPublished - 2006 Jul 1
Externally publishedYes


  • Carbon ion irradiation
  • Microarray
  • Oral squamous cell carcinoma
  • Pathway analysis
  • SPHK1

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research


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