Preliminary research on the pathological role of cathepsin-B in subcutaneous heteroplastic pancreatic carcinoma in nude mice.
- Author:
Chong ZHANG
1
;
Jia-bang SUN
;
Da-chuan LIU
;
Ye-qing CUI
;
Shuang LIU
;
Hai-chen SUN
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Antineoplastic Agents; therapeutic use; Blotting, Western; Body Weight; Cathepsin B; antagonists & inhibitors; genetics; metabolism; physiology; Cell Line, Tumor; Dipeptides; therapeutic use; Female; Humans; In Vitro Techniques; Mice; Mice, Nude; Pancreatic Neoplasms; drug therapy; metabolism; Placenta Growth Factor; Pregnancy Proteins; genetics; metabolism; Reverse Transcriptase Polymerase Chain Reaction; Transplantation, Heterologous
- From: Chinese Medical Journal 2009;122(20):2489-2496
- CountryChina
- Language:English
-
Abstract:
BACKGROUNDCathespin-B (cath-B) is an important proteolytic enzyme involved in the disease course of invasion in many types of cancer. Cath-B expression in subcutaneous heteroplastic pancreatic carcinoma in nude mice has not been studied. We investigated the role of cath-B in a model of heteroplastic pancreatic carcinoma in BALB/c nude mice.
METHODSThirty-two six-week-old female BALB/c nude mice were equally divided into four groups. PANC-1 cells were inoculated subcutaneously in the left axillary region. Besides volume, weight of subcutaneous tumor, and change in body weight, cath-B expression in each group was measured by immunohistochemical staining, PCR and Western blotting. Its relationship to microvessel density (MVD), CD44v6, and placenta growth factor (PLGF) was also examined. CA-074Me, a specific inhibitor of cath-B, was injected intraperitoneally (i.p.) at different stages of tumor growth in group B and C. Gemcitabine (GEM), was also injected (i.p.) in group D to compare anti-tumor efficacy with CA-074Me.
RESULTSExpression of cath-B at different levels was related to tumor growth, MVD, and PLGF expression. In group A (control group), cath-B expression was enhanced more than that seen in other groups. CA-074Me clearly inhibited cath-B expression and tumor growth in group B. There was no difference between group C and D with respect to anti-tumor effect.
CONCLUSIONSCath-B correlates with the growth and angiogenesis of tumors, but not with the adhesion induced by CD44v6. CA-074Me clearly inhibited cath-B expression and demonstrated an anti-neoplastic and anti-angiogenesis effect.
