Bisphosphonate treatment inhibits the growth of prostate cancer cells.
Bisphosphonate treatment inhibits the growth of prostate cancer cells.
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发表时间：
2001-03
期刊：
影响因子：
11.2
通讯作者：
Margaret Lee;Eva M. Fong;Frederick R. Singer;R. Guenette
中科院分区：
文献类型：
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作者：
Margaret Lee;Eva M. Fong;Frederick R. Singer;R. Guenette
在患有癌症的患者中出现骨骼转移会导致各种临床并发症。双膦酸盐是一类具有有效骨吸收抑制活性的药物，在治疗和管理转移性骨病患者方面越来越有用。几项临床试验表明，双膦酸盐在治疗和管理晚期前列腺癌骨骼转移方面具有临床价值。目前，双膦酸盐发挥其活性的机制才刚刚开始被理解。我们在体外研究了双膦酸盐对前列腺癌细胞生长的影响。用帕米膦酸盐或唑来膦酸盐处理PC3、DU145和LNCaP细胞可显著降低这三种细胞系的生长。流式细胞术显示，帕米膦酸盐处理（100微米）在所有三种细胞系中均可诱导大量细胞死亡。相比之下，用唑来膦酸钠（100微米）治疗不会诱导细胞死亡，反而会对细胞增殖产生显著影响，这可以从G0-G1和S期细胞的大量增加中得到证明。虽然这两种药物在血清存在下都能降低前列腺癌细胞的生长，但唑来膦酸盐在这些条件下更有效，在5%胎牛血清存在下，剂量低至25微米时破坏生长。这些结果提出了一种有趣的可能性，即观察到的双膦酸盐治疗骨骼转移的临床应用可能部分源于直接抑制前列腺癌细胞在骨微环境中的生长。
The presence of skeletal metastases in patients suffering from cancer leads to a variety of clinical complications. Bisphosphonates are a class of drugs with a potent bone resorption inhibition activity that have found increasing utility in treating and managing patients with metastatic bone disease. Several clinical trials have demonstrated that bisphosphonates have clinical value in the treatment and management of skeletal metastases derived from advanced prostate cancer. Currently, the mechanism(s) through which bisphosphonates exert their activity is only beginning to be understood. We have studied the effects of bisphosphonate treatment on the growth of prostate cancer cell lines in vitro. Treatment of PC3, DU145, and LNCaP cells with pamidronate or zoledronate significantly reduced the growth of all three cell lines. Using flow cytometry, pamidronate treatment (100 microM) was shown to induce significant amounts of cell death in all three cell lines studied. In contrast, treatment with zoledronate (100 microM) did not induce cell death, instead exerting dramatic effects on cell proliferation, as evidenced by a major increase in cells present in the G0-G1 and S phase. Although both drugs reduced prostate cancer cell growth in the presence of serum, zoledronate was more potent under these conditions, disrupting growth at doses as low as 25 microM in the presence of 5% fetal bovine serum. These results raise the intriguing possibility that the observed clinical utility of bisphosphonates in managing skeletal metastases may in part derive from direct inhibition of prostate cancer cell growth in the bone microenvironment.