OBJECTIVEThe aim of this study was to elucidate the radiosensitizing mechanism of irisquinone (IQ) and evaluate the utility of F-fluorodeoxyglucose (F-FDG) and F-fluoromisonidazole (F-FMISO) PET/computed tomography (CT) in assessing the radiosensitizing effect of IQ.MATERIALS AND METHODSIn an in-vitro experiment, C6 rat glioma cells were treated with IQ, radiation, or both. The viability and radiosensitivity of C6 cells were detected using the MTT assay and clonogenic survival assay. The expression of hypoxia-inducible factor-1α (HIF-1α) was evaluated by real-time PCR and western blot. In an in-vivo experiment, C6 rat glioma cells were implanted into the right flank of rats and treated with IQ, radiation, both, or no treatment. F-FDG and F-FMISO PET/CT images were obtained before and after treatment. The expression of HIF-1α was detected by immunohistochemistry staining.RESULTSIn the in-vitro experiment, the results of the MTT assay showed that the half-inhibition concentration (IC50) of IQ for normoxic and hypoxic C6 tumor cells was 17.2 and 21.0 nmol/l, respectively. Clonogenic survival assay showed that IQ could improve the radiosensitivity of both normoxic and hypoxic C6 tumor cells. When the concentration of irradiation was 20% IC50 (4.2 nmol/l), the sensitive enhancement ratio of normoxic and hypoxic C6 tumor cells was 1.18 and 1.33, respectively. The mRNA and protein expression levels of HIF-1α decreased significantly when treated with IQ plus radiation compared with the other groups.In the in-vivo experiment, 24 or 48 h after different treatments, the maximum standardized uptake values (SUVmax) of F-FDG or F-FMISO uptake decreased in the radiation group and the IQ plus radiation group, whereas these values increased in the control and IQ groups. The SUVmax of F-FDG or F-FMISO uptake in IQ plus radiation group were lower than those of the radiation group (t=3.28, 2.62, P<0.05). However, there was no significant decrease in tumor volumes in the radiation group and the IQ plus radiation treatment group early after treatment.Immunohistochemistry staining showed that there were significant differences in the expression of HIF-1α in the four groups (F=87.1, P<0.01). The SUVmax of both F-FDG and F-FMISO uptake showed a significant correlation with the expression of HIF-1α. F-FMISO provided a higher correlation coefficient with HIF-1α than F-FDG (r=0.93, 0.82, P<0.01).CONCLUSIONThe present experiments indicated that IQ enhanced the radiosensitivity of C6 rat glioma cells both in vitro and in vivo. The primary mechanism of this radiosensitizing effect involves the downregulation of HIF-1α. F-FDG and F-FMISO PET/CT were sensitive and noninvasive for monitoring the early radiosensitizing effect of IQ. Meanwhile, F-FMISO PET/CT provided more information on the changes in tumor hypoxic status.

2013-03-01·Nuclear Medicine Communications4区 · 医学

Dynamic observation of the radiosensitive effect of irisquinone on rabbit VX2 lung transplant tumors by using fluorine-18-deoxyglucose positron emission tomography/computed tomography

4区 · 医学

Article

作者: Xu, Huiqin ; Yue, Qiao ; Sun, Guoping ; Wu, Qiang ; Tang, Hong ; Wang, Hui

OBJECTIVEWe studied the radiosensitizing effect of irisquinone on a VX2 lung transplant tumor model during three-dimensional radiotherapy using fluorine-18-deoxyglucose ((18)F-FDG) PET/computed tomography (PET/CT).MATERIALS AND METHODSThirty VX2 tumor-bearing rabbits were randomized into three groups: the radiotherapy group, the irisquinone+radiotherapy group, and the control group, each comprising 10 rabbits. (18)F-FDG PET/CT images were obtained to monitor the tumor/muscle (T/M) ratio of F-FDG uptake and the retention index (RI) before treatment, when the radiation dose reached 6, 12, and 18 Gy, and 1 week after radiotherapy. Tumor volume changes were also assessed. The management of the control group followed the same procedure.RESULTSAt all treatment time points, the tumor volume was significantly smaller in the treatment groups than in the control group. The 1 and 2 h T/M ratios and RIs decreased gradually when the radiation dose reached 12 or 18 Gy in the treatment groups, whereas these values increased continuously in the control group. One week after treatment, the 1 and 2 h T/M ratios increased in the treatment groups, although these values remained lower than those in the control group. The RIs of the radiotherapy and irisquinone+radiotherapy groups were 0.329±0.133 and 0.137±0.036, respectively. Histological evaluation revealed that tumor F-FDG uptake was strongly related to tumor cell density.CONCLUSIONF-FDG PET/CT was sensitive and noninvasive and could be used to monitor the radiosensitizing effects of irisquinone and the therapeutic efficacy of radiotherapy.

2005-04-01·Yao xue xue bao = Acta pharmaceutica Sinica

[Preparation, identification and inclusion actions of irisquinone hydroxypropyl-beta-cyclodextrin inclusion complex].

Article

作者: Tang, Li-hua ; Zhang, Xue-nong ; Gong, Jin-hong ; Zhang, Qiang ; Yan, Xue-ying

AIMTo perpare and identify irisquinone hydroxypropyl-beta-cyclodextrin inclusion complex (irisquinone-HP-beta-CD), as well as to study the inclusion mechanism and molecule stoichiometry between irisquinone and hydroxypropyl-beta-cyclodextrin.METHODSIrisquinone-HP-beta-CD was prepared by freeze-drying technique. The ratio of host and guest was also studied in inclusion process by mol gradient and continuing variational methods. At the same time, the inclusion complex was identified by X-ray diffraction (XRD) and differential scanning calorimetry (DSC).RESULTSIt was demonstrated that the solubility of irisquinone was enhanced markedly by inclusion with HP-beta-CD when stoichiometry was 2:1 of host and guest at 25 degrees C, 35 degrees C and 45 degrees C.CONCLUSIONThe solubility and stability of irisquinone could be increased by preparing the inclusion complex with hydroxypropyl-beta-cyclodextrin.

100 项与马蔺子素相关的药物交易

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