Research Papers:

Efficacy of granulocyte-macrophage colony-stimulating factor combined with metronomic paclitaxel in the treatment of Lewis lung carcinoma transplanted in mice

Nengping Zhu, Rongsheng Qin, Qin Zhang, Shaozhi Fu, Shanshan Liu, Yue Chen, Juan Fan _ and Yunwei Han

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Oncotarget. 2018; 9:4951-4960. https://doi.org/10.18632/oncotarget.23530

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Nengping Zhu1,*, Rongsheng Qin1,*, Qin Zhang2, Shaozhi Fu1, Shanshan Liu1, Yue Chen3, Juan Fan1 and Yunwei Han1

1Department of Oncology and the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China

2Department of Gastroenterology, First People’s Hospital of Liangshan Yi Autonomous Prefecture, Xichang, 615000, China

3Department of Nuclear Medicine, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China

*These authors have contributed equally to this work

Correspondence to:

Juan Fan, email: [email protected]

Yunwei Han, email: [email protected]

Keywords: lung cancer; paclitaxel; metronomic chemotherapy; GM-CSF; dendritic cell

Received: September 19, 2017     Accepted: December 04, 2017     Published: December 21, 2017


Metronomic chemotherapy in combination with immunotherapy is an attractive approach in cancer therapy. The purpose of the present study was to investigate the anti-tumor effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination with metronomic paclitaxel (MET PTX) on Lewis lung carcinoma transplanted in mice. In the present study, tumor-bearing mice survival time and tumor growth were monitored. The day after the end of the treatment, white blood cells were counted, and the number and maturation of dendritic cell were determined by flow cytometry. Besides, microvessel density and tumor cell proliferation were determined by immunohistochemistry, while apoptosis was determined by TUNEL (Terminal deoxynucleotidyl transferase-mediated nick end labeling) assay. Micro 18F-FDG PET/CT (18F-Fluorodeoxyglucose positron emission tomography/computed tomography) was used to obtain SUVmax values. White blood cells reduction was not observed in the mice treated with GM-CSF combined with MET PTX. Moreover, GM-CSF combined with MET PTX further reduced proliferation and microvessel density, promoted tumor apoptosis, increased the dendritic cells number and induced their maturation, with concomitant delay in tumor growth and improved survival. Taken together, GM-CSF combined with MET PTX exerted a synergistic anti-tumor effect against lung cancer in a mouse model through an antiangiogenic activity and inducing dendritic cells maturation without exerting pronounced adverse effects. Hence, combined metronomic chemotherapy and immunotherapy could be a potential strategy for the treatment of patients with advanced lung cancer.

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