肿瘤坏死因子辅佐骨肉瘤化疗的体外研究

A vitro study of chemotherapy of osteosarcoma enhanced by tumor necrosis factor

目的：探讨肿瘤坏死因子（ Ｔ Ｎ Ｆ）及其与阿霉素（ Ａ Ｄ Ｍ ）共同作用对骨肉瘤 Ｏ Ｓ７３２及耐药模型 Ｒ Ｏ Ｓ７３２细胞活性的影响。方法：应用阿霉素诱导建立 Ｒ Ｏ Ｓ７３２，用 Ｍ Ｔ Ｔ 法测定 Ｔ Ｎ Ｆ 及其与 Ａ Ｄ Ｍ 共同作用下 Ｏ Ｓ７３２及 Ｒ Ｏ Ｓ７３２细胞的存活率（ Ｃ Ｓ Ｒ）。结果： Ｒ Ｏ Ｓ７３２细胞表现出明显耐药，对 Ａ Ｄ Ｍ 耐药倍数达３０以上，且耐药表型 Ｐ１７０蛋白、 Ｇ Ｓ Ｔ、 Ｔ Ｏ Ｐ ＯⅡ呈强阳性表达。 Ｔ Ｈ Ｆ 单独作用，无论是 Ｏ Ｓ７３２还是 Ｒ Ｏ Ｓ７３２细胞，在１００ ｋ Ｕ／ｍ ｌ内 Ｃ Ｓ Ｒ 均在１００％ ， Ｔ Ｎ Ｆ 与 Ａ Ｄ Ｍ 共同作用后的 Ｃ Ｓ Ｒ 明显低于 Ａ Ｄ Ｍ 单独作用组，在 Ｒ Ｏ Ｓ７３２细胞更明显（ Ｐ＜ ０００５）。结论：单独应用 Ｔ Ｎ Ｆ在１００ ｋ Ｕ／ｍ ｌ内对骨肉瘤细胞活性无影响，而与 Ａ Ｄ Ｍ 联合应用则明显增加 Ａ Ｄ Ｍ 的抗肿瘤效应，在耐药细胞中表现更为明显。

Objective:To study the effect of tumor necrosis factor on the cytoactivity of human osteosarcoma cell line (OS 732) and its drug resistant models (R OS 732).Methods:Continuous incubation of human osteosarcoma cell lin(OS 732) with doxorubicin (ADM) of stepwise was increased in a small concentration to establish a multidrug resistant model (R OS 732) of human osteosarcoma cell line (OS 732) and detect the cytoactivity of OS 732 cells and R OS 732 cells after incubation with TNF accompanied and not accompanied by ADM through the method of MTT colorimeritric analysis and the cell survival rate (CSR) was expressed as cytoactivity.Results:R OS 732 cells were resistant to many different antitumor drugs;especially to ADM;the ratio of drug resistance was 30.The CSR of OS 732 cells and R OS 732 cells were the same with the value of 100% while incubation with TNF in dose of less than 100 000 u/ml only,but when they were incubated with TNF accompanied by ADM,the results were quite different: both for the OS 732 and R OS 732 cells the CSR was less than that of ADM only,and the later one was more obvious.Conclusion:TNF has no effect on the cytoactivity of both OS 732 and R OS 732 cells within the dose of 100 000 u/ml,but it could enhance the anti tumor effect of ADM,especially in drug resistant cells.