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Original Articles
- MDR1 Gene Expression and Chemosensitivity to Anticancer Drugs in SNU Hepatocellular Carcinoma Cell Lines
- In Gyu Hong, Sung Gyu Lee, Hyun Ju Lee, Gyung Hwa Him, Hun Sik Kim, Jae Gahb Park
- J Korean Cancer Assoc. 1994;26(2):219-231.
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Abstract
PDF - Using recently established 8 SNU human hepatocellular carcinoma cell lines and Hep 3B cell line, we performed in vitro chemosensitivity test using semiautomated tetrazolium-based colorimetric(MTT) assay. We also measured the MDRl gene expression of these cell lines by measuring MDR1 RNA level using slot blot analysis. IC values(concentration of chemotherapeutic agent which produces 50% growth inhibition of tested cells) were in the range of 1.92~5000 ↑ ug/ml for 5-fluorouracil, 0.24~32.00 ug/ml for doxorubicin, 0.16-10.29 pg/ml for mitomycin-c, 2.00~16.56 ug/ml for cisplatin, 1.15-182.32 ug/ml for etoposide, and 0.002 ↓L -24 ↑ug/ml for vincristine. Assay area under the curve(A-AUC) at IC: values showed that only A-AUC of VP-16 was in a clinically achievable range for only one of the 9 cell lines. All other drugs were out of the range of clinically achievabie AUC. Three cell lines(SNU-354, SNU-368, SNU-449) were MDR-positive. When these 3 cell lines were compared to MDR-negative cell lines, IC value for doxorubicin was significantly higher (P<0.05), suggesting that high expression of MDRl gene is responsible for doxorubicin resistance in hepatocellular carcinoma cell lines.
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- Expression of Multidrug Resistant Genes in Bone Marrow Mononuclear Cells of Patients with Myeloid Leukemia
- Seok Goo Cho, Il Ho Yang, Hyeon Seok Eom, Chang Gi Min, Hee Je Kim, Dong Wook Kim, Jong Wook Lee, Chi Wha Han, Woo Sung Min, Won Il Kim, Chun Choo Kim
- J Korean Cancer Assoc. 1999;31(1):153-164.
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Abstract
PDF
- PURPOSE
Multidrug resistance mediated by several drug resistant genes impedes the successful outcome of anti-cancer chemotherapy. In this study, we investigated the expressions of drug resistant genes encoding multidrug resistance (MDR1), multidrug resistance-associated protein (MRP), topoisomerase I (Topo I), topoisomerase II g (Topo II a) in narmal volunteers (n=12) in and patients with myeloid leukemia (n=34). Material and Method: We compared the levels of their transcripts in bone matrow mononuclear cells by semiquantitative RT-PCR. The amount of specific transcripts was represented as the optical density ratio of PCR product of target gene to that of B2- microglobulin (MG). Twenty patients of acute myelogenous leukemia (eight in remission state, twelve in refractory) and fourteen patients of chronic myelogenous leukemia (nine in chronic phase and five in blastic crisis) were examined. Twelve normal healthy persons were compared with leukemic patients.
RESULTS
The expression levels of all resistant genes in normal volunteers were relatively high as those of AML patients. Regardless of the disease status including remission status of AML (complete remission versus refractory) and the phase of CML (chronic phase versus blastic phase), the expression levels of all resistant genes in patients with CML were significantly lower than in the patients with AML (p < 0.05). Of interest, the patients with refractary AML did not show any statistical difference in comparison with normal controls and even the patients with AML in complete remission. Among the four drug resistant genes, the optical density ratio of MDRl was significantly lower than that of any other genes (p<0.05). Using HL-60 cell line, we compared the changes of various resistant gene expressions before and after differentiation induced by dimethylsulfoxide. The expressions of resistant genes declined in paralle1 with granulocytic differentiation, suggesting that the induction of cell differentiation might make leukemic cells susceptible to chemotherapeutic agents.
CONCLUSION
It is impossibble to explain the mechanism of drug resistance by comparing the level of drug resistant gene expression between nonnal subjects and patients with myeloid leukemias. Therefore, we suppose that longitudinal study of drug resistant gene expression is necessary to demonstrate the development of drug resistant during chemotherapy.
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