Potentiation of the antitumor activity by a novel quinoline compound, MS-209, in multidrug-resistant solid tumor cell lines.

Abstract

A novel quinoline compound, MS-209, was examined for its ability to reverse multidrug resistance (MDR) in several murine and human MDR solid tumor cell lines both in vitro and in vivo. MS-209 strongly reversed drug resistance to adriamycin (ADM) and vincristine (VCR) in acquired MDR tumor cell lines, 2780AD and KB-C1. In addition, MS-209 enhanced the cytotoxic effect of ADM and VCR on various human and murine cell lines. Particularly in 4-1St cells, which are extremely resistant to ADM and VCR, MS-209 at a concentration of 3 microM enhanced the cytotoxicity of ADM and VCR, 88- and 350-fold, respectively. MS-209 administered orally, together with ADM, enhanced the antitumor activity of ADM on Colon 26 and 4-1St tumors implanted subcutaneously (SC) in mice; the antitumor effect of ADM plus MS-209 was higher than that of ADM alone at the maximum tolerated dose (MTD). Furthermore, the coadministration schedules of MS-209 to attain the highest potentiation of ADM activity were examined using Colon 26 tumors. The maximum antitumor activity was obtained when MS-209 was administered on the same day as ADM. MS-209 administered a day before the ADM injection exhibited no potentiation effect, whereas MS-209 administered a day after the ADM injection showed a moderate effect. The effect of MS-209 was weaker when administered in a fractionated manner than when administered as a single dose. The results presented in this article suggest that MS-209 is an effective agent to overcome MDR in cancer chemotherapy.

• Authors: O Nakanishi, M Baba, A Saito, T Yamashita, W Sato, H Abe, N Fukazawa, T Suzuki, S Sato, M Naito, T Tsuruo
• Journal: Oncology research (Oncol Res) Vol. 9 Issue 2 Pg. 61-9 ( 1997) ISSN: 0965-0407 [Print] United States
• PMID: 9167187 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Quinolines
• dofequidar
• Vincristine
• Doxorubicin

Topics

• Adenocarcinoma (drug therapy, pathology)
• Animals
• Antineoplastic Agents (therapeutic use, toxicity)
• Cell Division (drug effects)
• Colonic Neoplasms (drug therapy, pathology)
• Colorectal Neoplasms (drug therapy, pathology)
• Doxorubicin (therapeutic use, toxicity)
• Drug Resistance, Multiple
• Drug Synergism
• Female
• Humans
• Melanoma, Experimental (drug therapy, pathology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred DBA
• Mice, Nude
• Quinolines (therapeutic use, toxicity)
• Stomach Neoplasms (drug therapy, pathology)
• Transplantation, Heterologous
• Tumor Cells, Cultured
• Vincristine (therapeutic use, toxicity)