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Iranian Journal of Basic Medical Sciences، جلد ۱۸، شماره ۶، صفحات ۵۹۹-۶۰۳
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عنوان انگلیسی Inhibition of janus kinase 2 by compound AG490 suppresses the proliferation of MDA-MB-231 cells via up-regulating SARI (suppressor of AP-1, regulated by IFN)
چکیده انگلیسی مقاله Objective(s): The Janus kinase-signal transducers and activators of transcription signaling pathway (JAK/STAT pathway) play an important role in proliferation of breast cancer cells. Previous data showed that inhibition of STAT3 suppresses the growth of breast cancer cells, but the associated mechanisms are not well understood. This study aims to investigate the effect and associated mechanisms of JAK/STAT pathway inhibitor AG490 on proliferation and suppression of breast cancer cells. Materials and Methods: CCK-8 assay and trypan blue exclusion assay were used to investigate the cytotoxicity of AG490 to MDA-MB-231 cells. Real-time PCR was used to detect the mRNA level of SARI (suppressor of AP-1, regulated by IFN). Western blot was used to analyze the protein levels of SARI, phospho-STAT3 and total STAT3. Luciferase reporter assay was adopted to explore the mechanism of SARI mRNA upregulation. Results: AG490 suppressed the proliferation of MDA-MB-231 cells in a dose-dependent manner. AG490 significantly up-regulated the mRNA and protein levels of SARI in MDA-MB-231 cells. Knockdown of SARI obviously attenuated AG490-induced growth suppression effect in MDA-MB-231 cells. Furthermore, AG490 dramatically enhanced the transcription activity of SARI promoter. But the transcription activity of truncated SARI promoter, which does not contain STAT3 binding site, cannot be activated by AG490 treatment. Conclusion: We demonstrate in this study that AG490 suppresses the proliferation of MDA-MB-231 cells through transcriptional activation of SARI.
کلیدواژه‌های انگلیسی مقاله AG490, MDA-MB-231, Proliferation, SARI, STAT3
نویسندگان مقاله یان خیا زانگ | yan xia zhang
department of radiation oncology, shandong cancer hospital, shandong university, jinan, shandong, china|department of radiation oncology, linyi people’s hospital, linyi, shandong, china


li یان | li yan
department of radiation oncology, linyi people’s hospital, linyi, shandong, china


guang yu liu | guang yu liu
department of traumatology, linyi people’s hospital, linyi, shandong, china


wen جون chen | wen jun chen
department of radiation oncology, linyi people’s hospital, linyi, shandong, china


wei hong gong | wei hong gong
department of radiation oncology, linyi people’s hospital, linyi, shandong, china


جین ming yu | jin ming yu
department of radiation oncology, shandong cancer hospital, shandong university, jinan, shandong, china
نشانی اینترنتی http://ijbms.mums.ac.ir/article_4538.html
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زبان مقاله منتشر شده en
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نوع مقاله منتشر شده Original Article
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