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TITLE:

A COMPREHENSIVE STUDY ON INTERACTION OF IMATINIB IN LUNG CANCER WITH TUMOR ASSOCIATED MACROPHAGES

AUTHORS:

Dr. Muhammad Mohsin Zia, Dr. Sajid Abbas, Dr. Muhammad Haseeb

ABSTRACT:

Introduction: Imatinib is a tyrosine kinase inhibitor and firstly used for Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML). It has also been found that Imatinib has therapeutic effect on several solid tumors. Aims and objectives: The basic aim of the study is to find the interaction of Imatinib in lung cancer with tumor associated macrophages. Methodology of the study: This cross sectional study was conducted at Allied Hospital Faisalabad during June 2019 to August 2019. Imatinib mesylate was obtained from Sigma-Aldrich and its solutions were prepared at the stock concentration of 50 mM (DMSO). Recombinant murine IL-13, IL-4 and M-CSF were purchased from PeproTech. LPS was also purchased from Sigma-Aldrich. Total RNA from RAW264.7 cells and BMDMs was isolated using Trizol (Invitrogen, CA, USA), and cDNA was synthesized using TransScript One-Step gDNA Removal and cDNA Synthesis SuperMix. Results: Given that STAT6 plays a key role in IL-13 or IL-4 induced macrophage M2-like polarization, we assessed whether STAT6 is involved in Imatinib inhibited M2 polarization. IL-13 markedly triggered the phosphorylation of STAT6 in 30 min, and reached a peak in 1 h, which was significantly restrained by Imatinib. Conclusions: It is concluded that Imatinib inhibits macrophage M2-like polarization both in vitro and in vivo which contributes to its anti-metastatic function in lung cancer.

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