TY - JOUR
T1 - Multidrug Resistance in Cultured Human Leukemia and Lymphoma Cell Lines Detected by a Monoclonal Antibody, MRK16
AU - Ishida, Yasushi
AU - Ohtsu, Tomoko
AU - Hamada, Hirofumi
AU - Sugimoto, Yoshikazu
AU - Tobinai, Kensei
AU - Minato, Keisuke
AU - Tsuruo, Takashi
AU - Shimoyama, Masanori
PY - 1989/10
Y1 - 1989/10
N2 - Forty cultured human leukemia and lymphoma cell lines never exposed to anticancer agents in culture, apart from doxorubicin (ADM)‐resistant K562/ADM, were examined for reactivity with a monoclonal antibody, MRK16 in F(ab′)2 form [MRK16‐F(ab′)2], which recognizes P‐glycoprotein (P‐gp). The relative resistance index to various drugs was calculated by dividing the 50% growth inhibitory concentration (IC50) of the test cell line by IC50 of K562, which was the negative control in the antibody experiment. MRK16‐F(ab′)2 reacted with four cell lines, K562/ADM, KYO‐1, HEL and CMK, which had relative resistance index values of 2 or more to vincristine (VCR), vindesine, vinblastine, ADM, daunorubicin, mitoxantrone (MIT), etoposide (VP‐16) and actinomycin‐D (ACT‐D). The level of resistance to VCR and ADM in these cell lines decreased significantly in the presence of 10 μM verapamil in vitro. Significant expression of mRNA of P‐gp gene was also detected in K562/ADM, KYO‐1 and HEL. MRK16‐F(ab′)2 did not react with 36 other cell lines. Among them, three cell lines, PL‐21, P31/FUJ and KOPM‐28, had relative resistance index values of 2 or more to anthracyclines, MIT and VP‐16, but not to vinca alkaloids or ACT‐D. The level of ADM‐resistance in these cell lines did not decrease significantly in the presence of 10 μM verapamil. Five cell lines, ATL‐1K, HL‐60, KMOE‐2, ML‐1 and U266, had relative resistance index values of 2 or more to some of the drugs, but not to the others, and 19 other cell lines did not. These results indicate that the reactivity of MRK16‐F(ab′)2 correlates with a relative resistance index of 2 or more to all these drugs in cultured human leukemia and lymphoma cell lines.
AB - Forty cultured human leukemia and lymphoma cell lines never exposed to anticancer agents in culture, apart from doxorubicin (ADM)‐resistant K562/ADM, were examined for reactivity with a monoclonal antibody, MRK16 in F(ab′)2 form [MRK16‐F(ab′)2], which recognizes P‐glycoprotein (P‐gp). The relative resistance index to various drugs was calculated by dividing the 50% growth inhibitory concentration (IC50) of the test cell line by IC50 of K562, which was the negative control in the antibody experiment. MRK16‐F(ab′)2 reacted with four cell lines, K562/ADM, KYO‐1, HEL and CMK, which had relative resistance index values of 2 or more to vincristine (VCR), vindesine, vinblastine, ADM, daunorubicin, mitoxantrone (MIT), etoposide (VP‐16) and actinomycin‐D (ACT‐D). The level of resistance to VCR and ADM in these cell lines decreased significantly in the presence of 10 μM verapamil in vitro. Significant expression of mRNA of P‐gp gene was also detected in K562/ADM, KYO‐1 and HEL. MRK16‐F(ab′)2 did not react with 36 other cell lines. Among them, three cell lines, PL‐21, P31/FUJ and KOPM‐28, had relative resistance index values of 2 or more to anthracyclines, MIT and VP‐16, but not to vinca alkaloids or ACT‐D. The level of ADM‐resistance in these cell lines did not decrease significantly in the presence of 10 μM verapamil. Five cell lines, ATL‐1K, HL‐60, KMOE‐2, ML‐1 and U266, had relative resistance index values of 2 or more to some of the drugs, but not to the others, and 19 other cell lines did not. These results indicate that the reactivity of MRK16‐F(ab′)2 correlates with a relative resistance index of 2 or more to all these drugs in cultured human leukemia and lymphoma cell lines.
KW - Culture cell
KW - Leukemia
KW - Lymphoma
KW - Monoclonal antibody
KW - Multidrug resistance
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U2 - 10.1111/j.1349-7006.1989.tb01641.x
DO - 10.1111/j.1349-7006.1989.tb01641.x
M3 - Article
C2 - 2575608
AN - SCOPUS:0024829330
SN - 1347-9032
VL - 80
SP - 1006
EP - 1013
JO - Cancer Science
JF - Cancer Science
IS - 10
ER -
