Establishment of radiotherapy combined with antisense bcl-2 oligodeoxynucleotide in prostate cancer

Bc1-2已被证明通过阻断细胞凋亡延长癌细胞存活，并具有清除活性氧的功能。反义bc1-2寡脱氧核苷酸（bc1-2 AS ODN）在PC-3细胞和JCA-1细胞中产生剂量依赖性细胞毒性和凋亡增加和bc1-2蛋白表达剂量依赖性降低。bcl-2 AS ODN显著增强了辐射对JCA-1细胞的细胞毒性，通过集落形成实验评估，与对照组（bcl-2感ODN或阳离子脂质）相比，己烯雌酚（DES）显著抑制PC-3细胞的生长，并呈剂量依赖性，显著诱导活性氧（ROS）的产生。反义bc1-2寡脱氧核苷酸显著增强des诱导的细胞毒性。bc1-2 AS ODN与DES联合使用比单独使用bc1-2 AS ODN和单独使用DES诱导的凋亡细胞明显增加。Buthionine sulphoximine （BSO）是一种谷胱甘肽消耗物，可显著降低细胞内谷胱甘肽浓度，增强des诱导的PC-3细胞毒性和ROS。bc1-2 AS ODN处理既不影响ROS的生成，也不影响细胞内谷胱甘肽浓度。综上所述，bc1-2 AS ODN通过凋亡途径显著增强了des诱导的非激素依赖性前列腺癌细胞的细胞毒性，而不需要增加活性氧的产生，而谷胱甘肽消耗物则增强了其细胞毒性和活性氧的产生

Bc1-2 has been shown to prolong cancer cell survival by blocking apoptosis and to have the function of scavenging reactive oxygen species. Antisense bc1-2 oligodeoxynucleotides (bc1-2 AS ODN) produced dose-dependent increases in cytotoxicity and apoptosis and a dose-dependent decrease in Bc1-2 protein expression in PC-3 cells and JCA-1 cells. Bc1-2 AS ODN significantly augmented the cytotoxicity induced by radiation on JCA-1 cells, which was assessed by the colony forming assay, when compared with controls (bcl-2 sense ODN or cationic lipid)Diethylstilbestrol (DES) significantly inhibited cell growth in PC-3 cells in a dose dependent fashion and significantly induced reactive oxygen species (ROS) generation. Antisense bc1-2 oligodeoxynucleotides significantly enhanced DES-induced cytotoxicity. A significant increase in apoptotic cells was induced by the combination of bc1-2 AS ODN and DES when compared with bc1-2 AS ODN alone and DES alone. Buthionine sulphoximine (BSO), which is a glutathione depletor, significantly decreased the intracellular concentration of glutathione and augmented the DES-induced cytotoxicity and ROS in PC-3 cells. Neither the generation of ROS nor the intracellular concentration of glutathione was influenced by bc1-2 AS ODN treatment. In conclusion, bc1-2 AS ODN significantly enhanced DES-induced cytotoxicity on hormone-independent prostate cancer cells through the apoptotic pathway, independently of an augmentation of reactive oxygen species generation, whereas the glutathione depletor augments its cytotoxicity and reactive oxygen species generation