scholarly journals High-lose and long-term therapy with interferon-alfa inhibits tumor growth and recurrence in nude mice bearing human hepatocellular carcinoma xenografts with high metastatic potential

Hepatology ◽  
2000 ◽  
Vol 32 (1) ◽  
pp. 43-48 ◽  
Author(s):  
Lu Wang ◽  
Zhao-You Tang ◽  
Lun-Xiu Qin ◽  
Xiao-Feng Wu ◽  
Hui-Chuan Sun ◽  
...  
2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Chao Liang ◽  
Zhebin Dong ◽  
Xianlei Cai ◽  
Jie Shen ◽  
Yuan Xu ◽  
...  

AbstractSorafenib, a multikinase inhibitor, is considered as the only approved drug to cure the advanced hepatocellular carcinoma (HCC); however, the acquired chemoresistance caused by intratumoral hypoxia through sorafenib long term therapy induces sorafenib inefficacy. We demonstrated here that hypoxia significantly attenuated sensitivity of HCC cells to sorafenib treatment and reduced its proliferation. Autophagy was observed in sorafenib-treated HCC cells in hypoxia, and inhibition of autophagy by 3-MA eliminated hypoxia-induced sorafenib resistance. Further study revealed hypoxia-activated FOXO3a, an important cellular stress transcriptional factor, via inducing its dephosphorylation and nuclear location; and FOXO3a-dependent transcriptive activation of beclin-1 was responsible for hypoxia-induced autophagy in HCC cells. Knockout of FOXO3a inhibited the autophagy induced by sorafenib itself in normoxia and significantly enhanced the cytotoxicity of sorafenib in HCC cells; and it also inhibited the hypoxia-induced autophagy and achieved the same effect in sorafenib sensitivity-enhancement in HCC cells as it in normoxia. Finally, knockout of intratumoral FOXO3a significantly enhanced curative efficacy of sorafenib via inhibition of autophagy in xenograft tumors in nude mice. Collectively, our study suggests that FOXO3a plays a key role in regulating hypoxia-induced autophagy in sorafenib-treated HCC, and FOXO3-targeted therapy may serve as a promising approach to improve clinical prognosis of patients suffering from HCC.


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Huimin Li ◽  
Dengzhao Jiang ◽  
Lei Zhang ◽  
Jiazhong Wu

A tumor growth model of human hepatocellular carcinoma HepG2 cells in nude mice was employed to investigate the antitumor activity of the total flavonoids extracted fromArachniodes exilis(TFAE)in vivo. Several biochemical assays including hematoxylin-eosin (HE) staining, immunohistochemistry, and Western blot were performed to elucidate the mechanism of action of total flavonoids extracted fromArachniodes exilis(TFAE). The results showed that TFAE effectively inhibited the tumor growth of hepatocellular carcinoma in nude mice and had no significant effect on body weight, blood system, and functions of liver and kidney. Expression levels of proapoptotic proteins Bax and cleaved caspase-3 remarkably increased while the expressions of Bcl-2, HIF-1α, and VEGF were suppressed by TFAE. These results suggested that the antitumor potential of TFEA was implied by the apoptosis of tumor cells and the inhibition of angiogenesis in tumor tissue.


2001 ◽  
Vol 7 (5) ◽  
pp. 597 ◽  
Author(s):  
Zhao-You Tang ◽  
Fan-Xian Sun ◽  
Jian Tian ◽  
Sheng-Long Ye ◽  
Yin-Kun Liu ◽  
...  

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