复制缺陷型腺病毒Ad-p14ARF治疗肝细胞癌的实验研究及作用机制的探讨

摘要

Objective: To study the therapeutic effect and mechanisms of recombinant adenovirus Ad-p14ARF in hepatocellular carcinoma cell lines. Methods: Morphology and trypan blue assay were adopted to evaluate the proliferation of different liver cancer cells after Ad-p14ARF infection. Cell apoptosis was confirmed by detecting phosphatidylserine (PS) externalization with Annexin V/PI double staining. Western blotting assay analyzed the expression of related proteins. Subcutaneous tumor model of BEL7402 was established to evaluate the therapeutic ability of Ad-p14ARF. Results: Ad-p14ARF suppressed cell growth, proliferation and promoted cell apoptosis of cancer cell lines with different genetic background. Ad-p14ARF inhibited growth of liver cancer cells (HepG2, BEL7402) in a dose-dependent manner. Ad-p14ARF leaded to overexpression of Bax and p21, which were the downstream regulating genes of p53. Ad-p14ARF suppressed tumor growth significantly in the experimental therapy in nude mice bearing subcutaneous tumor of BEL7402. Conclusion: P14ARF gene is a powerful tumor suppressor gene to be used in cancer gene therapy. It may play an important role in gene therapy against the malignancies in the future.