当前位置： SCI文献检索 > CANCER CHEMOTHERAPY AND PHARMACOLOGY期刊下所有文献 > Efficacy of SSG and SSG/IFNalpha2 against human prostate cancer xenograft tumors in mice: a role for direct growth inhibition in SSG anti-tumor action.

Efficacy of SSG and SSG/IFNalpha2 against human prostate cancer xenograft tumors in mice: a role for direct growth inhibition in SSG anti-tumor action.

Abstract：

BACKGROUND:Pre-clinical activity of SSG against melanoma and renal cancer has been identified recently although the drug's mechanism of action and activity against tumors of additional histological-types remain undefined. METHODS:The effects of SSG and SSG combination with other agents on DU145 human prostate carcinoma xenograft tumors in mice and on DU145 cell subpopulations of differential SSG sensitivities were evaluated. RESULTS:DU145 tumor growth was inhibited by SSG (69%), IFNalpha2 (33%) or the combination (80%) that induced complete regression of WM9 human melanoma tumors. DU145 cells in culture were also partially growth inhibited by SSG at killing doses (200-800 mug/ml) for WM9 cells, indicating a correlation of SSG inhibition of cancer cell growth in vitro and in vivo. DU145 cells formed multiple micro tumors in mice treated with SSG or SSG/IFNalpha2 in contrast to the single large tumors in the control or IFNalpha2-treated mice, suggesting the existence of an SSG-resistant subpopulation in DU145 cells. Indeed, DU145 but not WM9 cells formed colonies (approximately 4% frequency) when cultured in the presence of SSG. Single cell clone (DU145-7) isolated from DU145 cells showed SSG-resistant growth in culture, unassociated with cross-resistance to IFNalpha2 and converted to SSG-responsive cells by BSO that inhibited intracellular glutathione levels. CONCLUSIONS:These results implicate a role for direct growth inhibition in SSG anti-tumor action, provide novel insights into the mechanism of tumor resistance to the drug and suggest a therapeutic potential for SSG and its combinations with IFNalpha2 or BSO for prostate cancer that warrants further investigation.

journal_name

Cancer Chemother Pharmacol

journal_title

Cancer chemotherapy and pharmacology

authors

Li J,Lindner DJ,Farver C,Borden EC,Yi T

doi

10.1007/s00280-006-0378-3

subject

Has Abstract

pub_date

2007-08-01 00:00:00

pages

341-9

issue

3

eissn

0344-5704

issn

1432-0843

journal_volume

60

pub_type

杂志文章

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