Studies on Taxol Resistance Induced by HBx Viral Oncoprotein

There is increasing evidence since the effective chemotherapeutic potential of taxol has been shown in a variety ofcancers such as ovarian,breast and lung.However,chemotherapy with taxol often fails due to resistance of hepatocellular carcinoma (HCC). I attempted to determine the effect of taxolon HCC.Infection with hepatitis B virus (HBV)is a high risk factor for the development of HCC.Hepatitis B virus X (HBx)protein encoded by HBV genome is likely to play a important role in development of HBV-related HCC In addition, I explored the role of HBx underlying resistance to taxol in HCC. Treatment with taxol(100nM and 1uM)led to induce celldeath in Chang cells. However, the degree of death in ChangX-34 and ChangX-31 such as HBx expressing cell was weak than Chang cells. Next,we examined levels of Bcl-2 phosphorylation, which are known as molecule related taxol-induecd death. The phosphorylation levels of Bcl-2 increased in Chang cells, whereas the phosphorylation of Bcl-2 was reduced in ChangX-34 and ChangX-31 cells compare to Chang cells. Also, we found that the phosphorylation and expression levels of Bcl-2 were important in taxol response of HBV-related hepatoma cell lines,which were established from primary HCC tumors. Taxol-induced celldeath in Chang cells was triggered by caspase-independent cell death pathways. In contrast, celldeath in ChangX-31 and ChangX-34 was occurred by caspase-dependent cell death pathways. In addition, we found sulfasalazine, inhibitor of NF-κB activation, significantly increased cell death in ChangX-31 and ChangX-34 in a caspase-dependent manner but had not in fluence on Chang cells. Therefore, we conclude that HBx play an important role in taxol-resistance in HBV-related hepatoma. On the other hand, we suggest that sulfasalazine may be useful in the therapy of HBV-related hepatoma.

Author dc:creator

• 채, 선영

Contributors dc:contributor

• 조, 혜성
• 대학원 의학과
• 104913

• HCC
• HBx
• Taxol
• Bcl-2
• NF-κB
• Sulfasalazine

Language dc:language

ko

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000000787
000000000787

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/1517