36 respectively. Table 2 Semi-quantitative MK-1775 in vivo analysis of mdr1 and MRP in A549 cells, A549 MTS after irradiation, and MCF7/VCR cells Type of cells Mdr1/β2-MG MRP/β2-MG A549 parent cells in single-layer 0 0.76 A549 MTS 0 0.62
A549 MTS, d-9 after 15 Gy32P irradiation [11] 0 0.54 A549 MTS, d-9 after 15 Gy X-ray irradiation [11] 0 0.34 A549 MTS, d-4 after 30 Gy X-ray irradiation[6] 0 0.70 A549 re-proliferated radioresistant cells 0 0.78 MCF7/VCR resistant cells 35 4.36 Discussion In this study, re-proliferated cells derived from post-irradiated A549 lung adenocarcinoma MTS were used for an investigation of the disparity of drug Selleckchem LY2874455 sensitivity between the radioresistant cells and their parent cells. It is of great significance for the rational option of chemotherapeutic programs for relapsed cancer after mTOR inhibitor radiotherapy. The living cell number of A549 MTS became decreased after a medium dose of irradiation, and their mdrl and MRP gene expression levels examined by RT-PCR became temporarily reduced, subsequently showed little variation with their parent
cells after re-proliferated. In mono-layer culture, A549 re-proliferated radioresistant cell was resistant to DDP, but sensitive to VDS, 5-Fu, HCP, MMC and ADM. The sensitivity to the 6 kinds of chemotherapeutic drugs between the radioresistant cells and their parent cells were almost the same, but the radioresistant cells was resistant to high concentration of VPL, however their parent cells were sensitive to it. The mdrl and MRP multi-drug resistant gene expression in MCF7/VCR cells showed a very high level. Moreover, the cells which were resistant or had low sensitivity to a variety of chemotherapeutic agents showed a higher sensitivity to high concentration of VPL than A549 re-proliferated
radioresistant cells. VPL had not significant cell toxicity in a concentration of 10 μg/ml. It was found that a high concentration of VPL was needed for the in vitro reversion experiment of drug-resistance. In this article, the concentration of 200× PPC of VPL was used for in vitro experiment. If intra-arterial infusion or chemotherapeutic embolism were used for solid tumor, such a high local concentration can be achieved in the tumor without affecting the general dose and PPC in the body. According to Astemizole comparative analysis, the reduction of sensitivity of A549 re-proliferated radioresistant cells to VPL was not due to the levels of mdrl and MRP multidrug resistant genes. It has been reported in literature that the over-expression of GSH transferase (GST) pi protein in the MCF-7 cells after irradiation leads to an increase of VCR-resistance by 5-times, and the resistance to VP-16 increased by 3-times. In MCF-7 drug resistant sub-line, the selective resistance to some drugs may be related to an increase of the intracellular GST activity [15].
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