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Enhancement of cisplatin (DDP) antitumor activity by 3-aminobenzamide in rat ovarian tumors sensitive and resistant to DDP in vivo

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Summary

A cisplatin (DDP)-resistant rat ovarian tumor cell line (O-342/DDP) and its parental sensitive counterpart (O-342) were used to investigate the combination effect of DDP plus 3-aminobenzamide (3-AB), an inhibitor of adenosine diphosphate ribose transferase (ADPRT). Treatment with six doses of DDP in NMRI nude mice bearing O-342/DDP produced an increase in mean survival of only 1 day over that of controls (P >0.05). The addition of nontoxic doses of 3-AB (5 mM/kg × 6) increased the mean survival to 6.4 days compared with that obtained with DDP treatment alone (P <0.001). In the sensitive ovarian tumor line (O-342), the combination effect of DDP plus 3-AB was even more impressive: simultaneous treatment of NMRI nude mice bearing O-342 with three doses of DDP plus 3-AB increased the mean survival by 2 weeks and the median survival by 3 weeks over that achieved with DDP treatment alone. Possible mechanisms involved in the potentiation of DDP activity and the possible clinical potential of this combination are discussed.

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Abbreviations

3-AB:

3-aminobenzamide

ADP:

adenosine diphosphate

ADPRT:

adenosine diphosphate ribose transferase

BCNU:

1,3-bis-(2-chloroethyl)-1-nitrosourea

BSO:

d,l-buthionine-sulfoximine

DDP or cisplatin:

cis-diamminedichloroplatinum(II)

GSH:

reduced glutathione

MS:

median survival

NA:

nicotinamide

NAD:

nicotinamide-adenine dinucleotide

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Authors and Affiliations

  1. Institute of Toxicology and Chemotherapy, German Cancer Research Center, D-6900, Heidelberg, Federal Republic of Germany

    Guan Chen & W. Jens Zeller

  2. Cancer Institute, Sun Yatsen University of Medical Sciences, 510060, GuangZhou, P. R. China

    Guan Chen

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  1. Guan Chen
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  2. W. Jens Zeller
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Chen, G., Zeller, W.J. Enhancement of cisplatin (DDP) antitumor activity by 3-aminobenzamide in rat ovarian tumors sensitive and resistant to DDP in vivo. Cancer Chemother Pharmacol 26, 37–41 (1990). https://doi.org/10.1007/BF02940291

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