Hepatic Stellate Cell Coculture Enables Sorafenib Resistance in Huh7 Cells through HGFc-MetAkt and Jak2Stat3 Pathways
المؤلفون المشاركون
Jiang, Chunping
Chen, Weibo
Wang, Zhongxia
Ding, Yitao
Zhang, Guang
Wu, Junhua
Shi, Hua
Cao, Yin
المصدر
العدد
المجلد 2014، العدد 2014 (31 ديسمبر/كانون الأول 2014)، ص ص. 1-10، 10ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2014-06-25
دولة النشر
مصر
عدد الصفحات
10
التخصصات الرئيسية
الملخص EN
Purpose.
Tumor microenvironment confers drug resistance to kinase inhibitors by increasing RKT ligand levels that result in the activation of cell-survival signaling including PI3K and MAPK signals.
We assessed whether HSC-LX2 coculture conferred sorafenib resistance in Huh7 and revealed the mechanism underlying the drug resistance.
Experimental Design.
The effect of LX2 on sorafenib resistance was determined by coculture system with Huh7 cells.
The rescue function of LX2 supernatants was assessed by MTT assay and fluorescence microscopy.
The underlying mechanism was tested by administration of pathway inhibitors and manifested by Western blotting.
Results.
LX2 coculture significantly induced sorafenib resistance in Huh7 by activating p-Akt that led to reactivation of p-ERK.
LX2 secreted HGF into the culture medium that triggered drug resistance, and exogenous HGF could also induce sorafenib resistance.
The inhibition of p-Akt blocked sorafenib resistance caused by LX2 coculture.
Increased phosphorylation of Jak2 and Stat3 was also detected in LX2 cocultured Huh7 cells.
The Jak inhibitor tofacitinib reversed sorafenib resistance by blocking Jak2 and Stat3 activation.
The combined administration of sorafenib and p-Stat3 inhibitor S3I-201 augmented induced apoptosis even in the presence of sorafenib resistance.
Conclusions.
HSC-LX2 coculture induced sorafenib resistance in Huh7 through multiple pathways: HGF/c-Met/Akt pathway and Jak2/Stat3 pathway.
A combined administration of sorafenib and S3I-201 was able to augment sorafenib-induced apoptosis even in the presence of LX2 coculture.
نمط استشهاد جمعية علماء النفس الأمريكية (APA)
Chen, Weibo& Wu, Junhua& Shi, Hua& Wang, Zhongxia& Zhang, Guang& Cao, Yin…[et al.]. 2014. Hepatic Stellate Cell Coculture Enables Sorafenib Resistance in Huh7 Cells through HGFc-MetAkt and Jak2Stat3 Pathways. BioMed Research International،Vol. 2014, no. 2014, pp.1-10.
https://search.emarefa.net/detail/BIM-497032
نمط استشهاد الجمعية الأمريكية للغات الحديثة (MLA)
Chen, Weibo…[et al.]. Hepatic Stellate Cell Coculture Enables Sorafenib Resistance in Huh7 Cells through HGFc-MetAkt and Jak2Stat3 Pathways. BioMed Research International No. 2014 (2014), pp.1-10.
https://search.emarefa.net/detail/BIM-497032
نمط استشهاد الجمعية الطبية الأمريكية (AMA)
Chen, Weibo& Wu, Junhua& Shi, Hua& Wang, Zhongxia& Zhang, Guang& Cao, Yin…[et al.]. Hepatic Stellate Cell Coculture Enables Sorafenib Resistance in Huh7 Cells through HGFc-MetAkt and Jak2Stat3 Pathways. BioMed Research International. 2014. Vol. 2014, no. 2014, pp.1-10.
https://search.emarefa.net/detail/BIM-497032
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-497032
قاعدة معامل التأثير والاستشهادات المرجعية العربي "ارسيف Arcif"
أضخم قاعدة بيانات عربية للاستشهادات المرجعية للمجلات العلمية المحكمة الصادرة في العالم العربي
تقوم هذه الخدمة بالتحقق من التشابه أو الانتحال في الأبحاث والمقالات العلمية والأطروحات الجامعية والكتب والأبحاث باللغة العربية، وتحديد درجة التشابه أو أصالة الأعمال البحثية وحماية ملكيتها الفكرية. تعرف اكثر