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


CONCLUSIONS
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.
Li
Yu-Xiu
YX
Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100083, China.
Lin
Zhi-Bin
ZB
Tan
Huan-Ran
HR
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology; D016158:Genes, p53 / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation; D014750:Vincristine / Q000494:pharmacology
D000970:Antineoplastic Agents; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D014750:Vincristine; D017239:Paclitaxel; D005472:Fluorouracil