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| Novel Synergistic Anti-tumor Effects of DOX with Oncolytic Adenovirus ZD55-TRAIL on Hepatocellular Carcinoma Cells |
| LIU Tao, HAN Hua-feng, MA Bu-yun, YANG Yuan-qin, ZHUO Ling-yan, ZHOU Li, WANG Yi-gang |
| School of Life Sciences, Xinyuan Institute of Medicine and Biotechnology, Zhejiang Sci-Tech University, Hangzhou 310018, China |
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Abstract Doxorubicin hydrochloride, an antitumor antibiotic, exhibits prominent killing effects in numerous malignant tumours by suppressing the synthesis of genetic material of carcinoma cells. Nevertheless, the therapeutic effect with single drug is limited and the side-effect is very strong when the dose was added. The oncolytic adenovirus armed with cancer suppressor gene plays an important role in cancer therapy. However, there is little report for the treatment of liver cancers with the combination of oncolytic adenovirus ZD55 armed with Trail and doxorubicin hydrochloride. MTT assay and crystal violet assay were used to determine the growth inhibition effects of various treatments in hepatoma carcinoma cell Bel-7404; and Hoechst 33342 staining and flow cytometry assay were used to evaluate the cell apoptosis; with Western blotting assay to detect the trail and apoptosis-related protein expression; with immunofluorescence method and flow cytometry assay to detect the expression of apoptosis-related receptor. The results indicate that the combination therapy of oncolytic adenovirus ZD55 armed with Trail and doxorubicin hydrochloride could more significantly inhibited tumor cell proliferation and induce cell apoptosis compared with single drug. The cooperation mechanism of the two drugs refer to the expression level of the Trail receptor DR4 and DR5 was explored. The above primarily explored the mechanism of apoptotic inducement by the synergy treatments with DOX and ZD55-Trail, which provide the basis for further combinational treatment of hepatocellular carcinoma.
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Received: 19 November 2013
Published: 25 February 2014
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