Kaneski C R, Constantopoulos G, Brady R O
Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
Prostate. 1991;18(1):47-58. doi: 10.1002/pros.2990180105.
Dimethylsulfoxide (DMSO) modulates the tumorigenicity and other characteristics of some malignant cell lines in vitro. We have investigated DMSO effects on cell proliferation and glycosaminoglycan (GAG) synthesis in rat prostate adenocarcinoma (PAIII) cells in culture. DMSO inhibited cell proliferation and GAG synthesis and shedding. Cells that survived the initial exposure to 2.5% DMSO could be propagated in this concentration of the agent and were designated PAIII-DMSO resistant (PAIII-DMSOr). PAIII-DMSOr cells showed reversible indications of increased differentiation such as decreased growth rate and saturation density. Although the PAIII-DMSOr cells were grown in 2.5% DMSO, they had normal or elevated GAG content. The major GAG of both PAIII and PAIII-DMSOr cells was undersulfated heparan sulfate. Verapamil, a calcium channel blocker that reverses drug resistance in tumor cells, stimulated the growth of PAIII-DMSOr cells in the presence of 2.5% DMSO, but was inhibitory in the absence of DMSO. Growth of PAIII cells was inhibited by the differentiating agents sodium butyrate and retinoic acid and by the ionophore monensin. Interestingly, growth of PAIII-DMSOr cells in the presence of 2.5% DMSO was largely unaffected by sodium butyrate or retinoic acid. The results suggest that (1) PAIII-DMSOr cells arise from the induction of a compensation mechanism to DMSO effects in a preexisting population of cells: (2) there is a correlation between GAG synthesis and cell proliferation; and (3) further study of the verapamil effect may help elucidate the mechanism of the DMSO-induced differentiation of cancer cells.
二甲基亚砜（DMSO）在体外可调节某些恶性细胞系的致瘤性及其他特性。我们研究了DMSO对培养的大鼠前列腺腺癌细胞（PAIII）增殖及糖胺聚糖（GAG）合成的影响。DMSO抑制细胞增殖以及GAG的合成与释放。在最初暴露于2.5% DMSO后存活下来的细胞能够在该浓度的试剂中传代，并被命名为PAIII-DMSO抗性（PAIII-DMSOr）细胞。PAIII-DMSOr细胞表现出分化增强的可逆迹象，如生长速率和饱和密度降低。尽管PAIII-DMSOr细胞在2.5% DMSO中生长，但它们的GAG含量正常或升高。PAIII和PAIII-DMSOr细胞的主要GAG都是硫酸化不足的硫酸乙酰肝素。维拉帕米是一种可逆转肿瘤细胞耐药性的钙通道阻滞剂，在2.5% DMSO存在的情况下可刺激PAIII-DMSOr细胞生长，但在无DMSO时具有抑制作用。PAIII细胞的生长受到分化剂丁酸钠和视黄酸以及离子载体莫能菌素的抑制。有趣的是，在2.5% DMSO存在的情况下，PAIII-DMSOr细胞的生长在很大程度上不受丁酸钠或视黄酸的影响。结果表明：（1）PAIII-DMSOr细胞源于在预先存在的细胞群体中对DMSO效应诱导的一种补偿机制；（2）GAG合成与细胞增殖之间存在相关性；（3）对维拉帕米效应的进一步研究可能有助于阐明DMSO诱导癌细胞分化的机制。
