Wild type p53 increased chemosensitivity of drug-resistant human hepatocellular carcinoma Bel7402/5-FU cells

AIM: To study the effect of wild type (wt) p53 gene transfection on drug resistant human hepatocellular carcinoma (HCC) cells induced by 5-Fluorouracil (5-FU). METHODS: The cytotoxicity of anticancer drugs on Bel7402 and Bel7402/5-FU cells was assessed using SRB assay. p53 expression was detected at its mRNA level by RT-PCR assay and at its protein level Western blot or immunocytochemistry assay in Bel7402/5-FU cells transfected with either control vector or wt p53. AnnexinV-FITC/PI double labeled assay was performed to detect apoptosis. The chemosensitivity of Bel7402/5-FU cells transfected with wt p53 was assessed using SRB assay. RESULTS: Bel7402/5-FU cells exhibited cross-resistance to vincristine, doxorubicin, paclitaxel, and so on. wt p53 gene transfection upregulated the expression of p53 in Bel7402/5-FU cells. wt p53 was able to greatly inhibit cell proliferation and significantly induce apoptosis in Bel7402/5-FU cells. Moreover, wt p53 gene transfection increased the chemosensitivity of Bel7402/5-FU cells to some anticancer drugs. CONCLUSION: These results indicated that the wt p53 gene transfection not only induced suppression of cell growth, but also increased the sensitivity of Bel7402/5-FU cells to 5-FU, vincristine, and doxorubicin.