Shiao R T, Miglietta L, Khera S Y, Wolfson A, Freter C E
Division of Medical Oncology, Vincent T. Lombardi Cancer Research Center, Georgetown University Medical Center, Washington, DC 20007, USA.
Leuk Lymphoma. 1995 May;17(5-6):485-94. doi: 10.3109/10428199509056862.
Uncontrolled growth of neoplastic cells and unregulated production of immunoglobulin are major components of the morbidity and mortality of multiple myeloma. Suramin, a polysulfonated napthylurea, has antitumor activity in a number of malignancies, but also significant dose-related toxicity. Suramin has been reported to have major antiproliferative effects in a variety of lymphoid cell lines. Glucocorticoids have long been recognized to have activity in lymphoid malignancies and multiple myeloma while IL-6 has been reported to be an autocrine growth factor for multiple myeloma. This study examines growth inhibition and inhibition of IL-6-mediated secretion of immunoglobulin in human lymphoid and myeloma cell lines by dexamethasone and suramin. Dexamethasone and suramin show synergistic inhibition of cell proliferation at their IC10 concentrations. IL-6-mediated immunoglobulin secretion is also inhibited by both dexamethasone and suramin in an additive fashion. Both dexamethasone and suramin induce apoptosis of lymphoid cell lines, and suramin inhibits the binding of IL-6 to its receptor in a multiple myeloma cell line. These findings suggest that the synergistic growth inhibitory activities of dexamethasone and suramin may be related to induction of apoptosis by both agents and inhibition of IL-6-mediated autocrine growth stimulation and immunoglobulin production. These results indicate that the combination of low-dose suramin (in concentrations not associated with significant clinical toxicity) and dexamethasone merit further study in the treatment of myeloma or lymphoid malignancies.
肿瘤细胞的失控生长和免疫球蛋白的失调产生是多发性骨髓瘤发病和死亡的主要因素。苏拉明，一种多磺酸化萘脲，在多种恶性肿瘤中具有抗肿瘤活性，但也有显著的剂量相关毒性。据报道，苏拉明在多种淋巴细胞系中具有主要的抗增殖作用。长期以来，糖皮质激素被认为在淋巴系统恶性肿瘤和多发性骨髓瘤中具有活性，而白细胞介素-6据报道是多发性骨髓瘤的一种自分泌生长因子。本研究检测了地塞米松和苏拉明对人淋巴细胞系和骨髓瘤细胞系中细胞生长的抑制作用以及对白细胞介素-6介导的免疫球蛋白分泌的抑制作用。地塞米松和苏拉明在其IC10浓度时对细胞增殖表现出协同抑制作用。地塞米松和苏拉明对白细胞介素-6介导的免疫球蛋白分泌也呈相加性抑制。地塞米松和苏拉明均可诱导淋巴细胞系凋亡，苏拉明可抑制白细胞介素-6与其在骨髓瘤细胞系中的受体结合。这些发现提示，地塞米松和苏拉明的协同生长抑制活性可能与二者诱导凋亡以及抑制白细胞介素-6介导的自分泌生长刺激和免疫球蛋白产生有关。这些结果表明，低剂量苏拉明（浓度与显著临床毒性无关）与地塞米松联合应用在骨髓瘤或淋巴系统恶性肿瘤治疗中值得进一步研究。
