M2 macrophage inhibits the antitumor effects of Lenvatinib on intrahepatic cholangiocarcinoma

Background and objectives The relationship between the tumor microenvironment network of key signaling pathways in cancer plays a role occurrence development tumors. Tumor-associated macrophages (TAMs) are important inflammatory cells play an tumorigenesis progression. Macrophages malignant tumors, mainly M2 subtype, promote progression by producing cytokines down-regulating anti-inflammatory immune responses. Several articles have investigated effect on sensitivity chemotherapeutic agents, but few such been reported cholangiocarcinoma, so we macrophage cholangiocarcinoma to Lenvatinib compared M1. Methods THP-1 monocytes were polarized M0 phorbol 12-myristate 13-acetate (PMA) then induced differentiate into M1 LPS, IFN-γ IL-4 IL-13, respectively. co-cultured prior 24 hours administration, cell apoptosis was detected western-blot, FACS analysis Annexin V PI staining. Furthermore, use xCELLigence RTCA SP Instrument (ACEA Bio-sciences) monitor viability administration co-culture macrophages. After immunodeficient mice, administered, effects biological characteristics immuno-histochemistry. Results mRNA protein expression markers confirmed polarization derived macrophages, which provided successful efficient model monocyte TAMs. Lenvatinib-induced significantly reduced when with macrophage, whereas increased. In CDX model, markedly reduced, proliferative increased presence Angiogenesis related factors M2. Conclusion Compared M1, can inhibit anti-tumor through regulation, may be angiogenesis factor macrophage.