Multidrug resistance in cultured human leukemia and lymphoma cell lines detected by a monoclonal antibody, MRK16

Yasushi Ishida, Tomoko Ohtsu, Hirofumi Hamada, Yoshikazu Sugimoto, Kensei Tobinai, Keisuke Minato, Takashi Tsuruo, Masanori Shimoyama

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)1006-1013
Number of pages8
JournalJapanese Journal of Cancer Research
Volume80
Issue number10
Publication statusPublished - 1989 Oct
Externally publishedYes

Fingerprint

Multiple Drug Resistance
Lymphoma
Leukemia
Monoclonal Antibodies
Cell Line
Etoposide
Inhibitory Concentration 50
Mitoxantrone
P-Glycoprotein
Vincristine
Verapamil
Pharmaceutical Preparations
Vindesine
Vinca Alkaloids
Daunorubicin
Vinblastine
Anthracyclines
Dactinomycin
Antineoplastic Agents
Doxorubicin

Keywords

  • Culture cell
  • Leukemia
  • Lymphoma
  • Monoclonal antibody
  • Multidrug resistance

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Ishida, Y., Ohtsu, T., Hamada, H., Sugimoto, Y., Tobinai, K., Minato, K., ... Shimoyama, M. (1989). Multidrug resistance in cultured human leukemia and lymphoma cell lines detected by a monoclonal antibody, MRK16. Japanese Journal of Cancer Research, 80(10), 1006-1013.

Multidrug resistance in cultured human leukemia and lymphoma cell lines detected by a monoclonal antibody, MRK16. / Ishida, Yasushi; Ohtsu, Tomoko; Hamada, Hirofumi; Sugimoto, Yoshikazu; Tobinai, Kensei; Minato, Keisuke; Tsuruo, Takashi; Shimoyama, Masanori.

In: Japanese Journal of Cancer Research, Vol. 80, No. 10, 10.1989, p. 1006-1013.

Research output: Contribution to journalArticle

Ishida, Y, Ohtsu, T, Hamada, H, Sugimoto, Y, Tobinai, K, Minato, K, Tsuruo, T & Shimoyama, M 1989, 'Multidrug resistance in cultured human leukemia and lymphoma cell lines detected by a monoclonal antibody, MRK16', Japanese Journal of Cancer Research, vol. 80, no. 10, pp. 1006-1013.
Ishida, Yasushi ; Ohtsu, Tomoko ; Hamada, Hirofumi ; Sugimoto, Yoshikazu ; Tobinai, Kensei ; Minato, Keisuke ; Tsuruo, Takashi ; Shimoyama, Masanori. / Multidrug resistance in cultured human leukemia and lymphoma cell lines detected by a monoclonal antibody, MRK16. In: Japanese Journal of Cancer Research. 1989 ; Vol. 80, No. 10. pp. 1006-1013.
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abstract = "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.",
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AU - Ishida, Yasushi

AU - Ohtsu, Tomoko

AU - Hamada, Hirofumi

AU - Sugimoto, Yoshikazu

AU - Tobinai, Kensei

AU - Minato, Keisuke

AU - Tsuruo, Takashi

AU - Shimoyama, Masanori

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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.

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