Department of Clinical Sciences, Animal Cancer Center, Colorado State University, Fort Collins, CO 80523, USA.
Vet Comp Oncol. 2012 Mar;10(1):44-56. doi: 10.1111/j.1476-5829.2011.00274.x. Epub 2011 May 18.
Canine malignant histiocytosis (MH) is an aggressive neoplasm of macrophages and dendritic cells. It carries a poor prognosis because of the development of widespread metastasis and poor sensitivity to chemotherapy. Thus, there is a large need for new treatments for MH. We hypothesized that bisphosphonates might be useful to increase the effectiveness of cytotoxic chemotherapy against MH. To address this question, we conducted in vitro screening studies using MH cell lines and a panel of 6 chemotherapy and 5 bisphosphonate drugs. The combination of clodronate with vincristine was found to elicit synergistic killing which was associated with a significant increase in cell cycle arrest. Second, zoledronate combined with doxorubicin also significantly increased cell killing. Zoledronate significantly increased the uptake of doxorubicin by MH cells. On the basis of these findings, we conclude that certain bisphosphonate drugs may increase the overall effectiveness of chemotherapy for MH in dogs.
犬恶性组织细胞增生症（MH）是一种巨噬细胞和树突状细胞的侵袭性肿瘤。由于广泛转移的发展和对化疗的敏感性差，预后不良。因此，MH 需要新的治疗方法。我们假设双膦酸盐可能有助于提高细胞毒性化疗对 MH 的疗效。为了解决这个问题，我们使用 MH 细胞系和一组 6 种化疗药物和 5 种双膦酸盐药物进行了体外筛选研究。发现氯屈膦酸盐与长春新碱联合使用可产生协同杀伤作用，这与细胞周期停滞的显著增加有关。其次，唑来膦酸联合多柔比星也显著增加了细胞杀伤。唑来膦酸显著增加了 MH 细胞对多柔比星的摄取。基于这些发现，我们得出结论，某些双膦酸盐药物可能会提高犬 MH 化疗的总体疗效。
