Anti-PPARG monoclonal antibody, clone 9E2I9G5

Lung cancer is a heterogeneous disease in which patient-specific treatments are desirable and the development of targeted therapies has been effective. Although mutations in KRAS are frequent in lung adenocarcinoma, there are currently no targeted agents against KRAS. Using a mouse lung adenocarcinoma cell line with a Kras mutation (CMT167), we previously showed that PPARg activation in lung cancer cells inhibits cell growth in vitro yet promotes tumor progression when activated in myeloid cells of the tumor microenvironment. Here, we report that PPAR gamma activation in myeloid cells promotes the production of TGF beta 1, which, in turn, acts on CMT167 cancer cells to increase migration and induce an epithelial-mesenchymal transition (EMT). Targeting TGF beta 1 signaling in CMT167 cells prevented their growth andmetastasis in vivo. Similarly, anothermouse lung adenocarcinoma cell line with a Kras mutation, LLC, induced TGF beta 1 in myeloid cells through PPAR gamma activation. However, LLC cells are more mesenchymal and did not undergo EMT in response to TGF beta 1, nor did LLC require TGF beta 1 signaling for metastasis in vivo. Converting CMT167 cells to a mesenchymal phenotype through overexpression of ZEB1 made them unresponsive to TGF beta 1 receptor inhibition. The ability of TGF beta 1 to induce EMT in lung tumors may represent a critical process in cancer progression. We propose that TGF beta receptor inhibition could provide an additional treatment option for KRAS-mutant epithelial lung tumors.

Piperine is the main active component of Piper longum L., which is also the main component of anti-sciatica Mongolian medicine Naru Sanwei pill. It has many pharmacological activities such as anti-inflammatory and immune regulation. This paper aims to preliminarily explore the potential mechanism of piperine in the treatment of sciatica through network pharmacology and molecular docking. TCMSP, ETCM database and literature mining were used to collect the active compounds of Piper longumL. Swiss Target Prediction and SuperPred server were used to find the targets of compounds. At the same time, CTD database was used to collect the targets of sciatica. Then the above targets were compared and analyzed to select the targets of anti-sciatica in Piper longum L. The Go (gene ontology) annotation and KEGG pathway of the targets were enriched and analyzed by Metascape database platform. The molecular docking between the effective components and the targets was verified by Autodock. After that, the sciatica model of rats was established and treated with piperine. The expression level of inflammatory factors and proteins in the serum and tissues of rat sciatic nerve were detected by ELISA and Western blot. HE staining and immunohistochemistry were carried out on the sciatica tissues of rats. The results showed thatPiper longumL. can regulate the development of sciatica and affect the expressions of PPARG and NF-kB1 through its active ingredient piperine, and there is endogenous interaction between PPARG and NF-kB1. [GRAPHICS] .