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首页> 外文期刊>Oncology reports >Enhanced anti-tumor and anti-angiogenic effects of metronomic cyclophosphamide combined with Endostar in a xenograft model of human lung cancer
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Enhanced anti-tumor and anti-angiogenic effects of metronomic cyclophosphamide combined with Endostar in a xenograft model of human lung cancer

机译：节律性环磷酰胺联合Endostar在人肺癌异种移植模型中的增强抗肿瘤和抗血管生成作用

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Standard chemotherapy for advanced NSCLC has reached a therapeutic plateau. More effective strategies must be explored. The purpose of this study was to evaluate the role of metronomic chemotherapy combined with an angiogenesis inhibitor in non-small cell lung cancer (NSCLC). A total of 114 BALB/c nude mice were inoculated subcutaneously with human NSCLC cells (A549), and when xenograft tumors were palpable, mice were randomly injected with saline as controls (Ctrl), or treated with metronomic cyclophosphamide (MET CPA), recombinant human endostatin, Endostar (Endo), MET CPA combined with Endostar (MET CPA + Endo) or maximum tolerance dose of CPA (MTD CPA), respectively. The growth of xenograft tumors and mouse survival were monitored. The frequency of peripheral blood circulating endothelial cells (CECs), microvessel density (MVD) and pericyte coverage was determined using flow cytometry and immunofluorescence staining. In comparison with the controls, treatment with either drug significantly inhibited the growth of xenograft tumors in mice. Treatment with MET CPA or Endostar, but not with MTD CPA, significantly reduced the frequency of peripheral blood total and viable CECs and the value of MVD. Endostar also considerably reduced pericyte coverage in xenograft tumors. Moreover, MET CPA combined with Endostar further reduced the frequency of peripheral blood CECs, the value of MVD, and pericyte coverage, with concomitant delay in tumor growth and extension of mouse survival. Our results indicate that MET CPA combined with Endostar results in enhanced anti-tumor and anti-angiogenic effects in a xenograft model of human lung cancer. Combined therapy with metronomic chemotherapy and an angiogenesis inhibitor may serve as a promising treatment strategy for patients with advanced NSCLC.
机译：晚期NSCLC的标准化疗已达到治疗平台。必须探索更有效的策略。这项研究的目的是评估节律化疗联合血管生成抑制剂在非小细胞肺癌（NSCLC）中的作用。总共114只BALB / c裸鼠被皮下接种人NSCLC细胞（A549），当异种移植肿瘤可触知时，小鼠被随机注射生理盐水作为对照（Ctrl），或用节律性环磷酰胺（MET CPA）处理，重组人内皮抑素，Endostar（Endo），MET CPA联合Endostar（MET CPA + Endo）或CPA的最大耐受剂量（MTD CPA）。监测异种移植肿瘤的生长和小鼠存活。使用流式细胞仪和免疫荧光染色确定外周血循环内皮细胞（CEC）的频率，微血管密度（MVD）和周细胞覆盖率。与对照相比，用这两种药物治疗均能显着抑制小鼠异种移植肿瘤的生长。用MET CPA或Endostar进行治疗，但不使用MTD CPA进行治疗，可显着降低外周血总和存活CEC的频率以及MVD值。 Endostar还大大降低了异种移植肿瘤中周细胞的覆盖范围。而且，MET CPA与Endostar的结合进一步降低了外周血CEC的频率，MVD值和周细胞覆盖率，并伴随着肿瘤生长的延迟和小鼠存活期的延长。我们的结果表明，MET CPA与Endostar联合使用可在人肺癌异种移植模型中增强抗肿瘤和抗血管生成作用。结合节律化疗和血管生成抑制剂的联合治疗可能成为晚期NSCLC患者的有希望的治疗策略。

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