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Tissue‐specific growth suppression and chemosensitivity promotion in human hepatocellular carcinoma cells by retroviral‐mediated transfer of the wild‐type p53 gene
Author(s) -
Xu G W,
Sun Z T,
Forrester K,
Wang X W,
Coursen J,
Harris C C
Publication year - 1996
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510240546
Subject(s) - hepatocellular carcinoma , cancer research , genetic enhancement , viral vector , biology , cisplatin , cell culture , gene , cytotoxic t cell , liver cancer , microbiology and biotechnology , virology , in vitro , chemotherapy , genetics , recombinant dna
Selective expression of cytotoxic gene products in tumor cells is one of the goals of gene therapy for treating cancer. We are developing such a strategy for the treatment of human hepatocellular carcinoma (HCC) by linking the wild‐type p53 (WT‐p53) gene with HCC‐associated transcriptional control elements (TCE) to achieve selective growth inhibition of retrovirally transduced HCC cells. Replication‐defective, amphotrophic retroviruses were constructed containing a WT‐p53 complementary DNA (cDNA) that is transcriptionally regulated by the HCC‐associated α‐fetoprotein (AFP) gene TCE. Expression of exogenous WT‐p53 from this retroviral vector was limited to AFP‐producing cells. Introduction of WT‐p53 into AFP‐positive HCC cells by retroviral infection markedly inhibited their clonal growth in monolayer and soft agar cultures, and increased the sensitivity of these cells to the chemotherapeutic drug, cisplatin. Therefore, restoration of WT‐p53 expression in HCC cells, in combination with chemotherapeutic drugs, can be considered as a strategy for the therapy of human liver cancer.