化疗药物对分化脊索瘤细胞的影响。

The effects of chemotherapeutic agents on differentiated chordoma cells.

机构信息

Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, Istanbul.

出版信息

J Neurosurg Spine. 2011 Dec;15(6):620-4. doi: 10.3171/2011.7.SPINE10798. Epub 2011 Sep 9.

DOI:10.3171/2011.7.SPINE10798

PMID:21905773

Abstract

OBJECT

Chordoma is a rare type of malignant bone tumor and is known to arise from the remnants of the notochord. Resistance to chemotherapy makes the treatment of chordoma difficult; therefore, new approaches need to be developed to cure this disease. Differentiation therapy, using various differentiating agents, is attracting oncologists as a common therapeutic method to treat other tumors. Based on forcing cells to mature into other lineages, differentiation therapy might be an available method to treat chordomas in addition to conventional therapies.

METHODS

In this study a chordoma cell line, U-CH1, was exposed to several chemotherapeutic agents including vincristine, doxorubicin, cisplatin, etoposide, fludarabine, methotrexate, nilotinib, and imatinib mesylate under appropriate conditions. The first group of U-CH1 cells was exposed to drugs only and the second group of cells was exposed to the simultaneous treatment of 1 μM all-trans retinoic acid (ATRA) and chemotherapeutic agents in differentiation therapy. The efficacy of the differentiation method was assessed by measuring the viability of U-CH1 cells.

RESULTS

Vincristine, doxorubicin, etoposide, cisplatin, and fludarabine, each at a concentration of 10 μM, decreased the number of chordoma cells when given alone down to 11%, 0%, 30%, 67%, and 3%, respectively. Etoposide and cisplatin, each at a concentration of 10 μM, reduced the percentage of viable chordoma cells in a more effective way when given with 1 μM ATRA simultaneously, reducing the number of viable cells to 14% and 9%, respectively. On the other hand, imatinib and nilotinib, each at a concentration of 3 μM, as well as 10 μM methotrexate, showed no decrease in the number of cancer cells.

CONCLUSIONS

The results suggest that chordoma cells may be treated using the differentiation method in a more effective way than when they are treated with chemotherapeutic agents alone. This new approach may be an alternative method to conventional therapies in the treatment of chordoma.

摘要

目的

软骨肉瘤是一种罕见的恶性骨肿瘤，已知起源于脊索的残余物。对化疗的耐药性使得软骨肉瘤的治疗变得困难；因此，需要开发新的方法来治愈这种疾病。分化疗法，使用各种分化剂，作为治疗其他肿瘤的一种常见治疗方法，正吸引着肿瘤学家。基于迫使细胞成熟为其他谱系，分化疗法除了常规疗法之外，可能是治疗软骨肉瘤的一种可行方法。

方法

在这项研究中，软骨肉瘤细胞系 U-CH1 在适当的条件下分别暴露于几种化疗药物，包括长春新碱、阿霉素、顺铂、依托泊苷、氟达拉滨、甲氨蝶呤、尼罗替尼和甲磺酸伊马替尼。第一组 U-CH1 细胞仅暴露于药物，第二组细胞同时暴露于 1 μM 全反式视黄酸（ATRA）和化疗药物的分化治疗中。通过测量 U-CH1 细胞的活力来评估分化方法的疗效。

结果

长春新碱、阿霉素、依托泊苷、顺铂和氟达拉滨，浓度均为 10 μM，单独使用时，软骨肉瘤细胞数量分别减少到 11%、0%、30%、67%和 3%。当同时给予浓度为 10 μM 的依托泊苷和顺铂时，1 μM ATRA 可更有效地降低存活软骨肉瘤细胞的百分比，将存活细胞数量减少至 14%和 9%。另一方面，浓度分别为 3 μM 的伊马替尼和尼罗替尼以及 10 μM 甲氨蝶呤，没有降低癌细胞的数量。