Radio-resistance induced by nitric oxide to heavy ion irradiation in A172 human glioma cells

To investigate effects of nitric oxide on cellular radio-sensitivity, three human glioma cell lines, i.e. A172, A172 transfected green fluorescence protein (EGFP) gene (EA172) and A172 transfected inducible nitric oxide synthesis (iNOS) gene (iA72), were irradiated by C-12(6+) ions to 0, 1 or My. Productions of nitric oxide and glutathione (GSH) in A172, EA172 and iA172 were determined by chemical methods, cell cycle was analyzed by flow cytometry at the 24th hour after irradiation, and survival fraction of the cells was measured by colorimetric MTT assay at the 5th day after irradiation. The results showed that the concentrations of nitric oxide and GSH in iA172 were significantly higher than in A172 and EA172; the G(2)/M stage arrest induced by the C-12(6+) ion irradiation was observed in A172 and EA172 but not in iA172 at the 24th hour after exposure; and the survival fraction of iA172 was higher than that of EA172 and iA172. Data suggest that the radio-sensitivity of the A172 was reduced after the iNOS gene transfection. The increase of GSH production and the change of cellular signals such as the cell cycle control induced by nitric oxide may be involved in this radio-resistance.

BCNU-loaded PEG-PLLA ultrafine fibers and their in vitro antitumor activity against glioma C6 cells

The purpose of the present study was to develop implantable BCNU-toaded poly(ethylene glycol)poly(L-lactic acid) (PEG-PLLA) diblock copolymer fibers for the controlled release of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). BCNU was well incorporated and dispersed uniformly in biodegradable PEG-PLLA fibers by using electrospinning method. Environmental Scanning Electron Microscope (ESEM) images indicated that the BCNU-loaded PEG-PLLA fibers looked uniform and their surfaces were reasonably smooth. Their average diameters were below 1500 nm. The release rate of BCNU from the fiber mats increased with the increase of BCNU loading amount. In vitro cytotoxicity assay showed that the PEG-PLLA fibers themselves did not affect the growth of rat Glioma C6 cells. Antitumor activity of the BCNU-loaded fibers against the cells was kept over the whole experiment process, while that of pristine BCNU disappeared within 48 h. These results strongly suggest that the BCNU/PEG-PLLA fibers have an effect of controlled release of BCNU and are suitable for postoperative chemotherapy of cancers.