Maki A, Mohammad R, Raza S, Saleh M, Govindaraju K D, Pettit G R, al-Katib A
Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Anticancer Drugs. 1996 May;7(3):344-50. doi: 10.1097/00001813-199605000-00016.
It is crucial to incorporate new and more potent antineoplastic agents in treating non-Hodgkin's lymphoma since standard chemotherapy fails to cause a significant increase in the survival rate. A potential chemotherapeutic agent is dolastatin 10; hence, the objective of our study is to investigate the effect of the antiproliferative agent dolastatin 10 on different grades of non-Hodgkin's lymphoma cell lines. All cell lines exposed to dolastatin 10 initiated an apoptosis process. Alteration of oncogenes and their product may direct the entry of the cells into apoptosis, among these oncogenes are bcl-2 and c-myc. All cell lines tested expressed c-myc and bcl-2 proteins. However, 24 h after exposing the cell lines to 1 ng/ml dolastatin 10, bcl-2 expression was abolished but there was no significant change in c-myc protein expression. The contradictory roles of c-myc in cell proliferation and death require that other gene(s) products regiment the outcomes of c-myc activity on a cell. A possible candidate for such a modifying gene is bcl-2, whose product prolongs cell survival and blocks apoptosis. Given the above, dolastatin 10 induction of cell arrest is the initiating signal to downregulate the antiapoptotic bcl-2 and reactivate the apoptotic pathway. The reductions in bcl-2 may stabilize the c-myc proliferative action and induce apoptosis.
由于标准化疗未能显著提高生存率，因此在治疗非霍奇金淋巴瘤时加入新的、更有效的抗肿瘤药物至关重要。多拉司他汀10是一种潜在的化疗药物；因此，我们研究的目的是调查抗增殖剂多拉司他汀10对不同分级的非霍奇金淋巴瘤细胞系的影响。所有暴露于多拉司他汀10的细胞系都启动了凋亡过程。癌基因及其产物的改变可能会引导细胞进入凋亡，这些癌基因包括bcl-2和c-myc。所有测试的细胞系都表达c-myc和bcl-2蛋白。然而，在将细胞系暴露于1 ng/ml多拉司他汀10 24小时后，bcl-2表达被消除，但c-myc蛋白表达没有显著变化。c-myc在细胞增殖和死亡中的矛盾作用要求其他基因产物调节c-myc在细胞上的活性结果。bcl-2可能是这种修饰基因的一个候选者，其产物可延长细胞存活并阻止凋亡。鉴于上述情况，多拉司他汀10诱导细胞停滞是下调抗凋亡bcl-2并重新激活凋亡途径的起始信号。bcl-2的减少可能会稳定c-myc的增殖作用并诱导凋亡。
