In this article, the MRP -resistant gene expression level of A549 re-proliferated radioresistant cell showed no evident elevation, and the parent cells and radioresistant cells were resistant to DDP, which may be due to the increase of GST within the cells [14]. Whether the reduction of VPL sensitivity related to this condition is worthy Selleckchem Lazertinib of further investigation. VPL is a Ca2+ blocking agent inhibiting the elevation of intracellular calcium and reducing cell death. When the cellular concentration
of VPL is high, the drug sensitivity is elevated and consequently the cell death is enhanced. When the inflow of VPL to the radioresistant cells is decreased or the excretion is increased, the drug sensitivity is decreased. Whether the reduced sensitivity of radioresistant cells to VPL is attributable to the formation of protection protein on the surface of the membranous structure awaits further investigations. www.selleckchem.com/products/bix-01294.html Apoptosis is involved in Ca2+ flowing into the cytoplasm from endoplasmic reticulum, which can be inhibited by BCL-2. The BCL-2 protein expression is increased in the radioresistant cells [16, 17]. Whether the reduction of VPL toxicity is
related to the increase of BCL-2 protein is unknown. The pharmacological target of chemotherapeutic drug is DNA, but VPL affects the cell membrane and the calcium passage. It is postulated that, after repairing DNA damage induced by irradiation in A549 pulmonary AC220 adenocarcinoma MTS, some changes
in membrane proteins may occur. In addition, the MTT test showed that the A value of A549 parent cells was two times higher than their radioresistant cells, which illustrated that the re-proliferate ability of radioresistant cell may be reduced. As a result, the excretion of VPL is increased, leading to the development of VPL resistance. The detailed mechanism is currently unknown. VPL is generally accepted as a drug resistant reversion agent, but it seems that the radioresistance is different from the multiple drug resistance induced by chemotherapy, and that VPL is probably not an ideal reversion agent for radioresistant cells. Oxaprozin Therefore, new strategies need to be developed for the management of the relapse of radioresistant tumors in combination with chemotherapy. Acknowledgements This work was supported by the National Natural Science Foundation of China (No.30470497). The authors would like to thank Mr. Xiao-Dong He and Mr. Bin Su, whose efforts and contribution in this article for giving the radiation to multicellular spheroids of A549 lung adenocarcinoma in the Department of Radiation Oncology of Shanghai pneumology hospital. References 1. Welch DR, Aeed PA, Estrada J: Development and characterization of a rat model for locally recurring mammary tumors: sensitivities to 5-fluoro-2′-deoxyuridine, adriamycin, and X-irradiation. Cancer Res 1988, 48: 4549–4554.PubMed 2.