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目的:调节性T细胞(Regulatory T cells,Treg)被认为能够抑制抗肿瘤免疫反应,从而促进肿瘤生长。环磷酰胺(Cyclophosphamide,CTX)是个常规化疗药物,现在更多的注意力集中在其小剂量应用时可以删除Treg。了解小剂量环磷酰胺联合白细胞介素-2(Interleukin-2,IL-2)对4T1Balb/c乳腺癌荷瘤小鼠调节性T细胞的影响及其抗肿瘤效果。方法:通过皮下接种4T1乳腺癌细胞建立乳腺癌Balb/c荷瘤小鼠模型;20只荷瘤小鼠随机分为IL-2+NS组、PBS+CTX组、IL-2+CTX组及PBS+NS组,在种瘤第10天开始对荷瘤小鼠分别经腹腔按方案给药。在种瘤后第16天人道处死小鼠,采用流式细胞术检测小鼠脾脏中CD4+CD25+调节性T细胞数量,应用ELISA法检测血清干扰素-γ浓度,电子称称量肿瘤重量。结果:与对照组相比,在应用IL-2后,荷瘤小鼠脾脏CD4+CD25+/CD4+比值增加,在应用IL-2的同时使用小剂量CTX可减少CD4+CD25+/CD4+的比值;单次及联合用药均可提高血清INF-γ浓度;联合用药可减少肿瘤重量。结论:小剂量CTX可以减少由使用IL-2所增加的Treg数量,促进抗肿瘤免疫,提高IL-2的抗瘤效果,从而抑制肿瘤生长。该研究可能为乳腺癌的临床治疗提供一种有效的方法。
AIM: Regulatory T cells (Tregs) are thought to inhibit antitumor immune responses and thus promote tumor growth. Cyclophosphamide (CTX) is a conventional chemotherapeutic drug, and now more attention is focused on removing Tregs when used in small doses. To investigate the effects of low dose cyclophosphamide combined with interleukin-2 (IL-2) on regulatory T cells in 4T1Balb / c breast cancer-bearing mice and its anti-tumor effect. Methods: Balb / c tumor-bearing mice model was established by subcutaneous inoculation of 4T1 breast cancer cells. Twenty tumor-bearing mice were randomly divided into IL-2 + NS group, PBS + CTX group, IL- 2 + CTX group and PBS + NS group. The tumor-bearing mice were administered intraperitoneally on the 10th day after the tumorigenesis. The mice were sacrificed on the 16th day after the inoculation. The number of CD4 + CD25 + regulatory T cells in the spleen of mice was detected by flow cytometry. The serum IFN-γ concentration was measured by ELISA. The tumor weight was weighed electronically. Results: Compared with the control group, the proportion of CD4 + CD25 + / CD4 + increased in the spleen of the tumor-bearing mice after the application of IL-2, and the ratio of CD4 + CD25 + / CD4 + Times and combination therapy can increase serum INF-γ concentration; combination therapy can reduce tumor weight. Conclusion: Low-dose CTX can reduce the number of Tregs increased by using IL-2, promote antitumor immunity and enhance the anti-tumor effect of IL-2, thereby inhibiting tumor growth. This study may provide an effective method for the clinical treatment of breast cancer.