Resveratrol inhibits lung cancer growth by suppressing M2-like polarization of tumor associated macrophages.
In cancer, tumor associated macrophages (TAMs) play an important role in the cancer progression, evasion of immunity and dissemination of cancer cells. Inhibition of the activation or the M2 polarization of TAMs is an effective therapy for cancer. In the present study, we investigated the ability of resveratrol (RES) to inhibit lung cancer growth using in vitro and in vivo studies, and examined the underlying mechanisms. We demonstrated that M2 polarization of human monocyte derived macrophage (HMDMs) induced by the lung cancer cells conditioned medium was inhibited by RES. Additionally, RES exhibited inhibitory function in lung cancer cells co-cultured with human macrophages. The activity of signal transducer and activator of transcription 3 (STAT3) was significantly decreased by RES. Moreover, in a mouse lung cancer xenograft model, RES significantly inhibited the tumor growth, which was associated with inhibition of cell proliferation and decreased expression of p-STAT3 in tumor tissues. Further, RES inhibits F4/80 positive expressing cells and M2 polarization in the tumors. These results suggest that RES can effectively inhibit lung cancer progression by suppressing the protumor activation of TAMs.
Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Disease, Department of Intervention, Tianjin Huanhu Hospital, Tianjin 300060, PR China.
Liwei
L
Sun
Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Disease, Department of Intervention, Tianjin Huanhu Hospital, Tianjin 300060, PR China.
Bonian
B
Chen
Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Disease, Department of Intervention, Tianjin Huanhu Hospital, Tianjin 300060, PR China. Electronic address: rongjiango@126.com.
Rong
R
Jiang
Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Disease, Department of Intervention, Tianjin Huanhu Hospital, Tianjin 300060, PR China.
Jinduo
J
Li
Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Disease, Department of Intervention, Tianjin Huanhu Hospital, Tianjin 300060, PR China.
Bin
B
Wang
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D063646:Carcinogenesis; D002454:Cell Differentiation; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D000077185:Resveratrol; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*; D018418:Th2 Cells / Q000276:immunology; D019139:Tumor Escape; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D017077:Culture Media, Conditioned; D016207:Cytokines; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D013267:Stilbenes; D000077185:Resveratrol
Lung cancer; Macrophages; Resveratrol; STAT3