Kumar Chandan, Vats Kusum, Lohar Sharad P, Korde Aruna, Samuel Grace
Isotope Applications & Radiopharmaceuticals Division, Bhabha Atomic Research Centre , Mumbai, India .
Cancer Biother Radiopharm. 2014 Oct;29(8):317-22. doi: 10.1089/cbr.2014.1663. Epub 2014 Sep 16.
Lutetium-177 is an assured therapeutic radionuclide with favorable half-life and suitable β(-) energy. Radiolabeled (177)Lu-EDTMP (Ethylenediamine tetramethylene phosphonic acid) is by and large used for bone pain palliation in cancer patients. In vitro cell studies are carried out in osteosarcoma cells MG-63 to evaluate the combined effect of anticancer drug camptothecin (CPT) and (177)Lu-EDTMP. Two concentrations of (177)Lu-EDTMP (3.7 and 37 MBq) were incubated with MG63 cell line for 48 hours with and without pretreatment of CPT (10 nM) for 1 hour. After completion of incubation, the cells were harvested and cellular toxicity was estimated by LDH, MTT, and trypan blue dye. Apoptotic DNA fragmentation was estimated by ELISA kit. The expression of proteins such as bcl2, PARP, and MAPK (mitogen-activated protein kinase) that were related to apoptotic signaling pathways was assessed by western blotting. The results indicated that cellular toxicity and apoptosis were relatively higher in MG63 cells that were treated with CPT prior to treating with (177)Lu-EDTMP in comparison with the corresponding individual controls.
镥-177是一种有保障的治疗性放射性核素，具有良好的半衰期和合适的β(-)能量。放射性标记的(177)Lu-乙二胺四亚甲基膦酸（EDTMP）主要用于缓解癌症患者的骨痛。在骨肉瘤细胞MG-63中进行体外细胞研究，以评估抗癌药物喜树碱（CPT）和(177)Lu-EDTMP的联合作用。将两种浓度的(177)Lu-EDTMP（3.7和37 MBq）与MG63细胞系孵育48小时，分别有无CPT（10 nM）预处理1小时。孵育结束后，收获细胞，并通过乳酸脱氢酶（LDH）、噻唑蓝（MTT）和台盼蓝染料评估细胞毒性。通过酶联免疫吸附测定（ELISA）试剂盒评估凋亡DNA片段化。通过蛋白质印迹法评估与凋亡信号通路相关的蛋白质如bcl2、聚（ADP-核糖）聚合酶（PARP）和丝裂原活化蛋白激酶（MAPK）的表达。结果表明，与相应的单独对照组相比，在用(177)Lu-EDTMP处理之前先用CPT处理的MG63细胞中，细胞毒性和凋亡相对更高。
