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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2019.1
- 수록면
- 330 - 335 (6page)
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Hepatitis B virus (HBV) encoding the HBV x protein (HBx) is a known causative agent of hepatocellular carcinoma (HCC). Its pathogenic activities in HCC include interference with several signaling pathways associated with cell proliferation and apoptosis. Mutant C-terminal-truncated HBx isoforms are frequently found in human HCC and have been shown to enhance proliferation and invasiveness leading to HCC malignancy. We investigated the molecular mechanism of the reduced doxorubicin cytotoxicity by C-terminal truncated HBx. Cells transfected with C-terminal truncated HBx exhibited reduced cytotoxicity to doxorubicin compared to those transfected with full-length HBx. The doxorubicin resistance of cells expressing C-terminal truncated HBx correlated with upregulation of the ATP binding cassette subfamily B member 1(ABCB1) transporter, resulting in the enhanced efflux of doxorubicin. Inhibiting the activity of ABCB1 and silencing ABCB1 expression by small interfering ribonucleic acid (siRNA) increased the cytotoxicity of doxorubicin. These results indicate that elevated ABCB1 expression induced by C-terminal truncation of HBx was responsible for doxorubicin resistance in HCC. Hence, co-treatment with an ABCB1 inhibitor and an anticancer agent may be effective for the treatment of patients with liver cancer containing the C-terminal truncated HBx.
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참고문헌 (27)
참고문헌 신청
Liu N / 2015 / Msi1 confers resistance to TRAIL by activating ERK in liver cancer cells / FEBS Lett 589:897~903
Arzumanyan A / 2013 / Pathogenic mechanisms in HBV-and HCV-associated hepatocellular carcinoma / Nat Rev Cancer 13:123~135
Martin-Vilchez S / 2011 / The molecular and pathophysiological implications of hepatitis B X antigen in chronic hepatitis B virus infection / Rev Med Virol 21:315~329
Ng SA / 2011 / Hepatitis B virus X gene and hepatocarcinogenesis / J Gastroenterol 46:974~990
Kim CM / 1991 / HBx gene of hepatitis B virus induces liver cancer in transgenic mice / Nature 351:317~320
Arzumanyan A / 2013 / Pathogenic mechanisms in HBV-and HCV-associated hepatocellular carcinoma / Nat Rev Cancer 13:123~135
Martin-Vilchez S / 2011 / The molecular and pathophysiological implications of hepatitis B X antigen in chronic hepatitis B virus infection / Rev Med Virol 21:315~329
Ng SA / 2011 / Hepatitis B virus X gene and hepatocarcinogenesis / J Gastroenterol 46:974~990
Kim CM / 1991 / HBx gene of hepatitis B virus induces liver cancer in transgenic mice / Nature 351:317~320
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