title: Cyclooxygenase-2 inhibition attenuates hypoxic cancer cells induced m2-polarization of macrophages.
abstract: Tumor-associated macrophages (TAMs), represent a major subpopulation of tumor infiltrating immune cells. These alternatively activated M2-polarized macrophages are well known for their pro-tumor functions. Owing to their established role in potentiating tumor-neovasculogenesis and metastasis, TAMs have emerged as promising target for anti-cancer immunotherapy. One of the key TAMs related phenomenon that is amenable to therapeutic intervention is their phenotype switching into alternatively activated M2-polarized macrophages. Hindering macrophage polarization towards a pro-tumor M2 phenotype, or better still reprogramming the M2 like TAMs towards M1 subtype is being considered a beneficial anti-cancer strategy. Hypoxic tumor milieu has been proposed as one of the most plausible factor governing M2-polarization of macrophages. We recently demonstrated that hypoxic tumor cells imparted a pro—angiogenic M2 skewed phenotype to macrophages. Furthermore, sizeable body of data indicates for participation of cyclooxygenase-2 (COX-2) in macrophage polarization. Concordantly, inhibition of COX-2 is associated with impaired macrophage polarization. Prompted by this in the current study we decided to explore if inhibition of COX-2 activity via chemical inhibitors may prevent hypoxic cancer cell induced M2-polarization of macrophages. We observed that treatment with Flunixin meglumine, an established preferential inhibitor of COX-2 activity markedly inhibited hypoxic cancer cell induced of M2-polarization of macrophages thereby indicating for usage of COX-2 inhibition as possible anti-cancer treatment modality.
authors.affiliation: King George Medical University Department of Surgical Oncology Lucknow India.
authors.forename: P
authors.initials: P
authors.lastname: Dubey
authors.affiliation: Central Drug Research Institute Division of Toxicology Lucknow India.
authors.forename: R
authors.initials: R
authors.lastname: Shrivastava
authors.affiliation: Central Drug Research Institute Division of Toxicology Lucknow India.
authors.forename: C
authors.initials: C
authors.lastname: Tripathi
authors.affiliation: Central Drug Research Institute Division of Toxicology Lucknow India.
authors.forename: N K
authors.initials: NK
authors.lastname: Jain
authors.affiliation: King George Medical University Department of Surgical Oncology Lucknow India.
authors.forename: B N
authors.initials: BN
authors.lastname: Tewari
authors.affiliation: Central Drug Research Institute Division of Toxicology Lucknow India.
authors.forename: M-U-D
authors.initials: MU
authors.lastname: Lone
authors.affiliation: Central Drug Research Institute Division of Toxicology Lucknow India.
authors.forename: K S
authors.initials: KS
authors.lastname: Baghel
authors.affiliation: King George Medical University Department of Surgical Oncology Lucknow India.
authors.forename: V
authors.initials: V
authors.lastname: Kumar
authors.affiliation: King George Medical University Department of Surgical Oncology Lucknow India.
authors.forename: S
authors.initials: S
authors.lastname: Misra
authors.affiliation: Central Drug Research Institute Division of Toxicology Lucknow India smraticdri&commat;gmail.com.
authors.forename: S
authors.initials: S
authors.lastname: Bhadauria
authors.affiliation: Dr.R M L Institute of Medical sciences Department of Radiation Oncology Lucknow India drmlbhatt&commat;yahoo.com.
authors.forename: M L B
authors.initials: ML
authors.lastname: Bhatt
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply; D003002:Clonixin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000502:physiology; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C014558:flunixin meglumine; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D003002:Clonixin