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KMID : 0391319920020020193
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Korean Journal of Biological Response Modifiers
1992 Volume.2 No. 2 p.193 ~ p.200
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Modulation of Acquired Resistance to Adriamycin by Buthionine Sulfoximine
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홍원선
홍석일/김창민/이춘택/김유철/임영혁/이진오/강태웅
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Abstract
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The modulatory effects of buthionine sulfoximine (BSO), a specific inhibitor of glutathione synthesis, on the acquired resistance to adriamycin were investigated using MTT assay against human pulmonary adenocarcinoma cell line, PC-14, and its
subline
resistant to adriamycin, PC/ADM.. PC/ADM was developed by continuously exposing PC-14 to stepwise increasing doses of adriamycin and the limiting dilution technique PC/ADM was 4.40 times more resistant to adriamycin, in terms of IC50, than PC-14
in
MTT
assay The survivals of PC-14 and PC/ADM were not inhibited by 50 μM and 100μM of BSO PC/ADM WAS significantly inhibited by the addition of 50μM and 100μM of BSO to adriamycin compared to adriamycin alone, while PC-14 was not further inhibited
by the
addition of BSO than adriamycin alone. The modulatory effects of BSO on the resistance to adriamycin were evaluated in terms of IC50, dose modification factor (CMF: IC50 to adriamycin alone/IC50 to adriamycin plus BSO) and relative resistance
(RR:
IC50
of PC/ADM/IC50 of PC-14 )In PC-14, IC50 was not decreased by the addition of 50μM or 100μM of BSO to adriamycin compared with adriamycin alone. In PC/ADM, IC50 was significantly decreased by the addition of 50μM or 100μM of BSO to adriamycin
(p<0.01), however, IC50s of PC/ADM to adriamycin between 50μM and 100μM of BSO were not significantly different. DMFs of 50μM and 100μM of BSO in PC-14 were 0.93 and 1.18, repectively, indicating that BSO did not significantly modulate the
intrinsic
resistance to adriamycin in PC-14 However, in PC/ADM, 50μM 100 μM of BSO elevated DMF to 3.89 and 4.20 and 4.20, repectively, implicating that therapeutic efficacy for adriamycin might increase by a factor of 3.89 and 4.20, repectively, RR in
combination of adriamycin with 50μM and 100μM of BSO were 0.96 and 1.14, respectively, suggesting that the resistance of PC/ADM decreased to the level of PC-14 by the additional use of BSO. These results demonstrating that acquired resistance
to
adriamycin was significantly reversed by the addition of BSO suggest that BSO may be a potentially useful modulator of the acquired resistance to adriamycin.
Peripheral blood NK and LAK activity were measured with the 51Cr release against NK sensitive K562 and NK resistant Raji target cells. Twelve acute leukemia (8 on remission, 4 on diagnosis and relapse), 6 solid tumor (Rhabdomyosarcoma, Soft
sarcoma,
Wilms tumor, malignant lymphoma, Ganglioneuroblastoma, Retinblastoma), 4 brain tumor (Primitive Neuroectodermal tumor, Craniopharyngioma, Astrocytoma, Ependymoma) patients were tested.
NK activity of leukemic patients on diagnosis and relapse were low responder group, NK activity of leukemic patients on remission, 1 was high responder, 2 were medium responder, 5 were low responder, LAK activity of leukemic patients were low
responder
group.
NK activity of 3 out of 6 solid tumor patients were medium responder. LAK activity of leukemic patients were low responder group.
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KEYWORD
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