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.