促红细胞生成素对达卡巴嗪和顺铂抗小鼠黑色素瘤活性的调节作用

Erythropoietin modulates the anticancer activity of dacarbazine and cisplatin in a murine melanoma model

目的:研究促红细胞生成素(erythropoietin,EPO)对荷黑色素瘤小鼠肿瘤生长的影响及其对达卡巴嗪(dacarbazine,DTIC)和顺铂(cisplatin,DDP)抗肿瘤活性的调节作用。方法:将荷黑色素瘤B16细胞的C57BL/6小鼠,分别用EPO、DTIC和DDP以及EPO分别联合DTIC、DDP药物处理,以盐水处理组为对照。观察肿瘤在小鼠体内的生长情况。部分小鼠于停药次日摘除眼球取血,分析血液中红细胞(RBC)、血红蛋白(Hb)、红细胞压积(Hct)和白细胞(WBC)水平。并颈椎脱臼处死小鼠,剥离瘤体,分别称量瘤质量。其余小鼠用于生存期观察。结果:EPO处理组小鼠的肿瘤体积和质量与盐水处理组相比差异无统计学意义(P>0.05);DTIC联合EPO处理组小鼠的肿瘤体积和质量与DTIC处理组相比差异无统计学意义(P>0.05);DDP联合EPO处理组小鼠的肿瘤体积与DDP处理组相比明显缩小(P<0.05)。应用EPO处理组的小鼠外周血RBC、Hb和Hct水平明显高于未应用EPO组(P<0.05)。结论:EPO对黑色素瘤细胞在小鼠体内的生长没有明显影响;但EPO能调节黑色素瘤细胞对DTIC、DDP的敏感性,且该调节作用与化疗药的类型有关。

OBJECTIVE：The ability of erythropoietin（EPO）to regulate tumor growth and the anticancer activity of dacarbazine（DTIC）and cisplatin（DDP）was assessed in a murine melanoma model.METHODS：C57BL/6 mice were inoculated with melanoma cell line B16 and treated with EPO alone,the designated chemotherapeutic drug（DTIC or DDP）alone,or EPO and the drug,mice treated with saline was designated as control.Tumor growth and tumor appearance were assessed daily.The day after stopping the drugs,eye balls were removed and whole blood collected in EDTA-containing tubes from some mice,the blood was used to analyze the levels of red blood cell（RBC）,hematocrit（Hct）,hemoglobin（Hb）and white blood cell（WBC）.Subsequently,mice were sacrificed and the tumors were separated from the surrounding muscles and skin,and weighed.The remaining mice were used to study survival time.RESULTS：Tumor volume and weight of mice injected with EPO alone was not different compared to tumor-bearing animals injected with saline（P〉0.05）.Mice treated with EPO and DTIC was not different in tumor volume compared to those injected with DTIC alone（P〉0.05）.A significantly greater reduction in tumor mass was observed in EPO and cisplatin group compared to the group treated with cisplatin alone（P〈0.05）.Blood analysis indicated that a significant increase in RBC,Hct,and Hb was found in animals injected with EPO compared to animals that was not treated with EPO（P〈0.05）.CONCLUSION：EPO alone could not effect melanoma growth engrafted in mice.EPO could modulate the antitumor activity of various chemotherapeutic agents in melanoma-bearing mice,and the effect was drug related.