This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lee, W.-P. Articles by Hung, M.-C. Search for Related Content PubMed PubMed Citation Articles by Lee, W.-P. Articles by Hung, M.-C.

Adenovirus Type 5 E1A Sensitizes Hepatocellular Carcinoma Cells to Gemcitabine¹

Department of Internal Medicine [W-P. L., S-D. L.] and Cancer Center [Y. C.], Taipei Veterans General Hospital, Taipei, Taiwan; The Liver Research Unit, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan [D-I. T., S-L. T., C-T. Y.]; Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030 [M-C. H.]; and Department of Biochemistry, Yang-Ming University, Taipei, Taiwan [W-P. L.]

Hepatocellular carcinoma (HCC) is resistant to conventional chemotherapy. A few clinical trials have shown that the cytidine analogue gemcitabine appears to have antitumor activity for HCC, but the overall survival times remain to be improved. In this study, we examined the synergistic effect of adenovirus type 5 E1A (E1A) and gemcitabine on HCC and found that E1A sensitized J5, J7, Huh7, and HepG2 HCC cells to gemcitabine. To further study the E1A-mediated chemosensitization, we established stable cell lines that expressed the E1A gene and then examined whether E1A could have proapoptotic activity while expressed in HCC cells. Our results clearly showed that E1A sensitized HCC cells to gemcitabine through induction of apoptosis. To study the underlying mechanism, we tested nuclear factor (NF)-B activity and found that NF-B was activated in HCC cells treated with gemcitabine but not in HCC cells that expressed E1A. Occurrence of apoptosis entails cleavage of poly (ADP-ribose) polymerase (PARP), a nuclear protein involved in DNA repair, genome stability, and maintenance of telomere length. Our study showed that gemcitabine enhanced PARP expression. However, E1A did not induce PARP cleavage but rather suppressed PARP expression at the transcriptional level. Further study showed that both NF-B and PARP played protective roles in the prevention of E1A+gemcitabine-induced apoptosis.

This article has been cited by other articles:

				W.-P. Lee, D.-I. Tai, K.-H. Lan, A. F.-Y. Li, H.-C. Hsu, E.-J. Lin, Y.-P. Lin, M.-L. Sheu, C.-P. Li, F.-Y. Chang, et al. The -251T Allele of the Interleukin-8 Promoter Is Associated with Increased Risk of Gastric Carcinoma Featuring Diffuse-Type Histopathology in Chinese Population Clin. Cancer Res., September 15, 2005; 11(18): 6431 - 6441. [Abstract] [Full Text] [PDF]