Document Detail


Antitumor and normal cell protective effect of PKC412 in the athymic mouse model of ovarian cancer.
MedLine Citation:
PMID:  17127735     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
N-benzoyl-staurosporine (PKC412) is a selective inhibitor of protein kinase C, and it inhibits the growth of human cancer cells. In this study, we examined the antitumor effect of PKC412, given singly and in combination with paclitaxel, on tumor regression and chemotherapeutic side effects by assessing tumor burden and cytokine production responses in vivo. Twenty-six nude mice intraperitoneally inoculated with SKOV3 cells were treated differently in 4 treatment groups: PKC412 plus paclitaxel (n = 7), paclitaxel-only (n = 6), PKC412-only (n = 6), and controls (n = 7). At autopsy, we found that PKC412 itself slightly reduced the mass of tumor but did not fully inhibit tumor formation. The incidence of evident disease was decreased when PKC412 was combined with paclitaxel (43%). From the body weight of the tumor-bearing mice, we observed that PKC412 plus paclitaxel treated mice were less wasted than paclitaxel-only treated mice (18.1 g vs 22.4 g, p = 0.001). We measured intracellular TNFalpha, IFNgamma, IL-4, and IL-10 in stimulated mouse splenocytes using flow cytometry to determine if PKC412 inhibited cytokine production in T cells. TNFalpha, IFNgamma, and IL-10 production were all significantly inhibited in the paclitaxel-treated mice. The inhibitory effects on cytokine production by paclitaxel were compensated with PKC412 combination (p = 0.008, 0.035, 0.014, respectively). From this study, we deduce that PKC412 may have clinical applications in promoting tumor regression in ovarian cancer when combined with paclitaxel. Moreover, PKC412 is able to prevent weight loss and immunosuppression induced by paclitaxel because it rescues normal proliferating cells from cytotoxic effects.
Authors:
Myungshin Kim; In-Yang Park; Jihyang Lim; Yonggoo Kim; Ku Taek Han; Won Heui Chung; Kyungja Han
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Annals of clinical and laboratory science     Volume:  36     ISSN:  0091-7370     ISO Abbreviation:  Ann. Clin. Lab. Sci.     Publication Date:  2006  
Date Detail:
Created Date:  2006-11-27     Completed Date:  2007-01-09     Revised Date:  2014-08-08    
Medline Journal Info:
Nlm Unique ID:  0410247     Medline TA:  Ann Clin Lab Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  455-60     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / drug therapy*,  pathology
Animals
Antineoplastic Agents / pharmacology*
Body Weight / drug effects
Cell Line, Tumor
Cytokines / metabolism
Drug Therapy, Combination
Female
Humans
Mice
Mice, Inbred BALB C
Mice, Nude
Ovarian Neoplasms / drug therapy*,  pathology
Paclitaxel / pharmacology
Protein Kinase C / antagonists & inhibitors*
Spleen / drug effects,  metabolism
Staurosporine / analogs & derivatives*,  pharmacology
Xenograft Model Antitumor Assays*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Cytokines; 120685-11-2/4'-N-benzoylstaurosporine; 33069-62-4/Paclitaxel; EC 2.7.11.13/Protein Kinase C; H88EPA0A3N/Staurosporine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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