Back to Search
Start Over
Hyaluronan inhibits postchemotherapy tumor regrowth in a colon carcinoma xenograft model.
- Source :
-
Molecular cancer therapeutics [Mol Cancer Ther] 2010 Nov; Vol. 9 (11), pp. 3024-32. Date of Electronic Publication: 2010 Sep 10. - Publication Year :
- 2010
-
Abstract
- Bone marrow hypoplasia and pancytopenia are among the most undesirable sequelae of chemotherapy for the treatment of cancer. We recently showed that hyaluronan (HA) facilitates hematopoietic recovery in tumor-free animals receiving chemotherapeutic agents. However, following a chemotherapeutic regimen in tumor-bearing animals, it is possible that residual tumor cells might respond to systemic injections of HA. Thus, in this study, we investigated the effect of HA on the regrowth of residual tumor cells following chemotherapy. As a model, we used the HCT-8 human colon carcinoma cell line, which expresses the HA receptor CD44, binds exogenous HA, and is susceptible to a chemotherapy protocol containing irinotecan and 5-fluorouracil in a human/mouse xenograft model. HCT-8 cells were implanted in severe combined immunodeficient mice, followed by irinotecan/5-fluorouracil treatment. After three rounds of chemotherapy, residual tumors were allowed to regrow in the presence or absence of HA. The dynamics of tumor regrowth in the group treated with HA was slower compared with the control group. By week 5 after tumor implantation, the difference in the size of regrown tumors was statistically significant and correlated with lower proliferation and higher apoptosis in HA-treated tumors as compared with controls. This finding provides evidence that HA treatment does not stimulate but delays the growth of residual cancer cells, which is an important parameter in establishing whether the use of HA can enhance current chemotherapeutic strategies.<br /> (©2010 AACR.)
- Subjects :
- Animals
Carcinoma pathology
Cell Line, Tumor
Cell Proliferation drug effects
Chemotherapy, Adjuvant
Colonic Neoplasms pathology
Cytostatic Agents administration & dosage
Cytostatic Agents pharmacology
Drug Administration Schedule
Female
Humans
Hyaluronic Acid administration & dosage
Mice
Mice, SCID
Models, Biological
Xenograft Model Antitumor Assays
Carcinoma drug therapy
Colonic Neoplasms drug therapy
Hyaluronic Acid pharmacology
Neoplasm Recurrence, Local prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 1538-8514
- Volume :
- 9
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Molecular cancer therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 20833754
- Full Text :
- https://doi.org/10.1158/1535-7163.MCT-10-0529