ABSTRACT
<p><b>OBJECTIVE</b>To explore the inhibitory effect of arsenic trioxide (A(s2)O3) on the growth of rat C6 glioma cells (C6 cells) as well as finding out the feasibility of using As2O3 as chemotherapy of gliomas.</p><p><b>METHOD</b>C6 cells were treated by different dose of As2O3 (1, 2, 4, 6 and 8 micromol L(-1)). MTT assay and staining for PCNA were used for cell proliferation. Cell apoptosis was determined by TUNEL method and Bcl-2 expression was studied by Western blot. Parental rat C6 cells (5 x 10(5)/15 microL) were implanted into right caudate nucleus of male SD rats as control group. Rats bearing cerebral C6 gliomas as treated group were treated with 1 mmol x L(-1) As2O3. The general manifestation, survival time, MRI dynamic scanning and histopathological changes of all rats were observed.</p><p><b>RESULT</b>All the treated cells showed decreased proliferation in vitro as detected by MTT method (P < 0.01) and staining for PCNA. In situ labeling apoptotic DNA fragment of the treated cells demonatrated that the cell apoptosis significantly increased following treatment with As2O3 (P < 0.01). Western blot showed that the expression of Bcl-2 protein was decreased. All rats in control group died of cerebral gliomas within 3 weeks after implantation of C6 cells (17.8 +/- 0.92) d. Eight out of 10 rats in treated group died within 24-36 days (32.1 +/- 1.35) d and other 2 ones kept alive beyond 120 days with one treated rat being totally disappear of the tumor foci and another having a little residue of tumor.</p><p><b>CONCLUSION</b>The result demonstrates the potential efficacy of As2O3 in the treatment of gliomas. It also suggests that As2O3 may be a good candidate for chemotherapy of human gliomas.</p>
Subject(s)
Animals , Male , Rats , Arsenicals , Pharmacology , Cell Line, Tumor , Cell Proliferation , Down-Regulation , Glioma , Drug Therapy , Oxides , Pharmacology , Rats, Sprague-DawleyABSTRACT
Objective To explore the gene expression of interleukin-13 receptor (IL-13R)?2 and its relationship to proliferation activity of human gliomas.Methods The gene expression of IL-13R?in 50 hu- man gliomas,2 malignant human glioma cell lines and 6 normal brain tissues were studied by RT-PCR.Ki-67 labeling index (Ki267 LI) of all sample were detecteded by immunohistochemical staining.Results Only one normal brain tissues expressed very low IL-13R?2 mRNA,whereas 35 (70%) of 50 human brain tumors expressed 1L-13R?2 mRNA.The positive rate and expression level of IL-13R?2 mRNA were increased with the ascending of WHO tumor grade.(former:rs=0.87;letter:rs=0.69,P＜0.01).The difference of posi- tive rate and expression level of IL-13R 2?mRNA between the low grade and high grade tumors was statistical- ly significant,the proliferation activity of gliomas evaluated by Ki-67LI (Ki-67 Labeling Index,Ki-67LI) was positively correlated with IL-13R?2 gene expression and the tumor grade.Conclusion In human cerebral gliomas,IL-13R?2 genes may play an role in the malignant progression.The expression level of malignancy in molecular level and selecting the target of gene therapy.
ABSTRACT
<p><b>OBJECTIVE</b>To study the mechanism involved in the control of glioma cell proliferation with transfection of connexin (Cx) 43 gene.</p><p><b>METHODS</b>C6 rat glioma and TJ905 human glioblastoma cell lines without Cx43 gene expression were transfected with Cx43cDNA mediated by lipofectamine. Northern blot, in situ hybridization and immunohistochemical technology were used to detect the expression of Cx43mRNA and its protein with MTT assay and silver colloid stain for the detection of cell proliferation, TUNEL method for determination of cell apoptosis, scrape loading dye transfer (SLDT) for GJIC, Western blot and immunohistochemical technology for bFGF, PDGF, EGFR, IGF-I and IGFBP3 expression.</p><p><b>RESULTS</b>Cx 43 gene transfected glioma cells showed decreased proliferation, restored GJIC and decreased bFGF, PDGF, IGFBP3, except EGFR expression and cell apoptosis which showed no change.</p><p><b>CONCLUSION</b>The mechanism of Cx 43 gene inhibiting gliomas cell proliferation is the restoration of GJIC and decreased autocrine growth factors.</p>