Objective To Study the dose response relationships of murine tumor and normal tissue in fractionated carbogen plus low concentration oxygen radiotherapy (CPLCOR). Methods The experiments included three groups: air, carbogen (95%O 2+5%CO 2), and carbogen plus low concentration oxygen (10%O 2+85%N 2+5%CO 2), five fractions were given to animals using a biological equivalence dose formula. The transplantable spontaneous tumor LA759 in inbred T739 mice was used for tumor response studies and the skin radiation reaction was evaluated with Douglas and Fowler grading method. Results In fractionated schedule, the sensitivity enhancement ratios (SER) were 1.34 and 1.64 for CPLCOR and carbogen alone groups respectively. In skin response, the CPLCOR group showed a relatively milder reaction than the carbogen group did: their SER were 1.19 and 1.49 and the therapeutic gain factors (TGFs) for fractionated schedule were 1.13 and 1.10 respectively. Conclusions Compared with the results of single dose studies, TGF decreases during fractionated irradiation, indicating that the CPLCOR has fewer advantage than carbogen radiotherapy.
Diacetyldianhydrogalactitol (DADAG) is a member of the hexitols which shows a significant anticancer effect. Despite the fact that the antitumor effects of DADAG have been studied in a number of cell lines, the mechanism of its action remains unclear. Herein, we explored antitumor effects of DADAG and the possible mechanisms by which it inhibited the growth of human hepatocellular carcinoma cell QGY-7,703 and its derived xenograft tumors. Cell proliferation was evaluated with the sulforhodamine B assay in vitro. The results suggested that DADAG had mild antiproliferative activity on QGY-7,703 cells. The antitumor effect of DADAG was assessed in nude mice xenografted with QGY-7,703 cells. We found that DADAG significantly inhibited the tumor growth. Flow cytometry results indicated that the retarded cell proliferation is associated with increased G2/M cell cycle arrest. Further studies showed that the induced G2/M cell cycle arrest is, at least partially, attributed to an upregulation of cyclin B1, phospho-cell division cycle 2 (cdc2) (Thr), phospho-cdc2 (Thr), and cdc25c protein expression, and a decrease in cdc2 protein expression. Taken together, our data show that DADAG has mild proliferative effects on QGY-7,703 cells in vitro, but it significantly inhibits the growth of QGY-7,703 in a xenograft model in vivo. The modulation of several cell cycle progression regulation proteins responsible for G2/M phase transition may account for its antitumor effects.
A newly synthesized dithiocarbamate derivative, 4-methylpiperazine-1-carbodithioc-acid-3-cyano-3,3-diphenylpropyl ester hydrochloride (TM208), has demonstrated anticancer effects with low toxicity in earlier studies; however, the mechanism has yet to be identified. We explored antitumor effects of TM208 and the possible mechanisms by which it inhibited the growth of human hepatocellular carcinoma cell line QGY-7703 xenograft tumors. Cell proliferation was evaluated with the sulforhodamine B assay in vitro. The results suggested that TM208 had slightly antiproliferative activity on QGY-7703 cells. The antitumor effect of TM208 was assessed in nude mice xenografted with QGY-7703 tumors. We found that TM208 significantly inhibited tumor growth but did not cause loss of body weight or leukocytopenia. Western blotting was used to detect the expression of protein kinase C alpha, mitogen-activated protein kinase signal pathways, and cell cycle-related proteins. The results showed that TM208 decreased the expression of protein kinase C alpha, phospho-extracellular signal-regulated kinase-1/2, phospho-p38, cyclin B1, cell division cycle 2 (cdc2), and phospho-cdc2 (Thr161) and increased the expression of phospho-cdc2 (Tyr15). Taken together, our data show that TM208 has little antiproliferative effect on QGY-7703 cells in vitro, whereas it significantly inhibits the growth of QGY-7703 xenograft tumors with low toxicity in vivo. The inhibition of mitogen-activated protein kinase signal pathways and the regulation of the G2/M phase may be responsible for its antitumor effects.
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