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KMID : 0614619930250020352
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Korean Journal of Gastroenterology
1993 Volume.25 No. 2 p.352 ~ p.362
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In Vitro Combination Chemosensitivity Test for Hepatocellular Carcinoma Cell Line
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유내춘
정재복/김주항/박인서/김승수/조재용/최진혁/임호영/노재경
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Abstract
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Primary hepatocellular carcinoma(HCC) is one of the most common malignancies in Korea due mainly to high incidence of chronic hepatitis B virus infection. Most of the HCC are inoperable even at first presentation. So chemotherapy could be one of
the
major therapeutic modalities, but HCC is seldom chemosensitive. This type of chemoresistance is explainesd by high level of expression of multidrug resistance(MDR) gene and p-glycoprotein.
We initiated this study to establish the in vitro model of drug selection and combination for HCC. Three human HCC cell lines and five cytotoxic drugs were used. MTT assays for cytotoxicity test were performed with single chemotherapeutic agent
and
various two drug combinations. Slot blot analysis for measuring the expression levels or MDR1 RNA was performed and demon strated that 2 HCC lines show moderate to high degree of MDR1 expression.
The ranges of drug concentration which causes 50% inhibition of the cell lines (IC50) are in the clinically achievable concentrations for the 5-fluorouracil in two HCC lines, and adriamycin in one cell line. Two cell lines which showed positive
MDRI
expression were resistant to adriamycin, But all three cell lines were sensitive to etoposide irrespective of MDR1 expression. In the clinically achievable concentration ranges those we tested, singnificantly improved cytotoxic effects are
demonstrated
in combinations of etoposide plus cisplatin, and etoposide plus mitomycin-C out of 10 possible two drug combinations.
These data indicate the need for in vivo triais with the combination chemotherapy of etoposide plus cisplatin or etoposide plus mitomycin-C for HCC.
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