Farnesol inhibits tumor growth and enhances the anticancer effects of bortezomib in multiple myeloma xenograft mouse model through the modulation of STAT3 signaling pathway

2015 ◽  
Vol 360 (2) ◽  
pp. 280-293 ◽  
Author(s):  
Jong Hyun Lee ◽  
Chulwon Kim ◽  
Sung-Hoon Kim ◽  
Gautam Sethi ◽  
Kwang Seok Ahn
Endocrinology ◽  
2013 ◽  
Vol 154 (8) ◽  
pp. 2936-2947 ◽  
Author(s):  
Won Gu Kim ◽  
Jeong Won Park ◽  
Mark C. Willingham ◽  
Sheue-yann Cheng

Abstract Recent epidemiological studies provide strong evidence suggesting obesity is a risk factor in several cancers, including thyroid cancer. However, the molecular mechanisms by which obesity increases the risk of thyroid cancer are poorly understood. In this study, we evaluated the effect of diet-induced obesity on thyroid carcinogenesis in a mouse model that spontaneously develops thyroid cancer (ThrbPV/PVPten+/− mice). These mice harbor a mutated thyroid hormone receptor-β (denoted as PV) and haplodeficiency of the Pten gene. A high-fat diet (HFD) efficiently induced the obese phenotype in ThrbPV/PVPten+/− mice after 15 weeks. Thyroid tumor growth was markedly greater and survival was significantly lower in ThrbPV/PVPten+/− mice fed an HFD than in controls fed a low-fat diet (LFD). The HFD increased thyroid tumor cell proliferation by increasing the protein levels of cyclin D1 and phosphorylated retinoblastoma protein to propel cell cycle progression. Histopathological analysis showed that the frequency of anaplasia of thyroid cancer was significantly greater (2.6-fold) in the HFD group than the LFD group. The HFD treatment led to an increase in parametrial/epididymal fat pad and elevated serum leptin levels in ThrbPV/PVPten+/− mice. Further molecular analyses indicated that the HFD induced more aggressive pathological changes that were mediated by increased activation of the Janus kinase 2-signaling transducer and activator of transcription 3 (STAT3) signaling pathway and induction of STAT3 target gene expression. Our findings demonstrate that diet-induced obesity exacerbates thyroid cancer progression in ThrbPV/PVPten+/− mice and suggest that the STAT3 signaling pathway could be tested as a potential target for the treatment of thyroid cancer.


Oncotarget ◽  
2013 ◽  
Vol 5 (3) ◽  
pp. 634-648 ◽  
Author(s):  
Kodappully Sivaraman Siveen ◽  
Nurulhuda Mustafa ◽  
Feng Li ◽  
Radhamani Kannaiyan ◽  
Kwang Seok Ahn ◽  
...  

2010 ◽  
Vol 16 (23) ◽  
pp. 5781-5795 ◽  
Author(s):  
Jakob Weissenberger ◽  
Maike Priester ◽  
Christian Bernreuther ◽  
Stefanie Rakel ◽  
Markus Glatzel ◽  
...  

2019 ◽  
Vol 8 (17) ◽  
pp. 7345-7358 ◽  
Author(s):  
Shangyu Wang ◽  
Hongzhi Hu ◽  
Binlong Zhong ◽  
Deyao Shi ◽  
Xiangcheng Qing ◽  
...  

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