Combined SN-38 and gefitinib treatment promotes CD44 degradation in head and neck squamous cell carcinoma cells

Autor: Hiroshi Sakagami, Kumi Nanbu, Toshiyuki Nanbu, Emika Ohkoshi, Jun Shimada, Naoki Umemura
Rok vydání: 2017
Předmět:
0301 basic medicine
Oncology
Cancer Research
Metastasis
Mice
chemistry.chemical_compound
0302 clinical medicine
Antineoplastic Combined Chemotherapy Protocols
biology
Cell Cycle
Drug Synergism
Gefitinib
General Medicine
Cell cycle
Hyaluronan Receptors
Head and Neck Neoplasms
030220 oncology & carcinogenesis
Carcinoma
Squamous Cell
medicine.drug
medicine.medical_specialty
Cell Survival
SN-38
Irinotecan
03 medical and health sciences
Cell Line
Tumor
Internal medicine
medicine
Animals
Humans
neoplasms
Cell Proliferation
Oncogene
Squamous Cell Carcinoma of Head and Neck
Cell growth
business.industry
CD44
medicine.disease
Xenograft Model Antitumor Assays
Head and neck squamous-cell carcinoma
030104 developmental biology
chemistry
Proteolysis
Quinazolines
Cancer research
biology.protein
Camptothecin
Lysosomes
business
Zdroj: Oncology Reports.
ISSN: 1791-2431
1021-335X
Popis: The aim of the present study was to search for an effective regimen among existing chemotherapies for head and neck squamous cell carcinoma (HNSCC). Among the tested drugs, we focused on combined SN-38, which is the active metabolite produced from irinotecan hydrochloride - a type I DNA topoisomerase inhibitor - after it is metabolized by carboxylesterase in the liver and gefitinib, an EGFR tyrosine kinase inhibitor treatment, based on the ability of this combination to inhibit HNSCC cell growth. Contrary to our expectation, in vivo, there was no significant difference in tumor growth suppression between gefitinib-only treatment and gefitinib plus SN-38. However, when tumor measurements were continued after treatment ceased, we found that several tumors showed renewed growth in the gefitinib-only group. The tumors that resumed growing after treatment showed increased CD44 expression compared with tumors from the combined treatment group. Next, we investigated the mechanism whereby SN-38 and gefitinib inhibited CD44 expression in vitro. These studies revealed that the combined treatment promoted lysosomal degradation of CD44. The present study revealed that combined gefitinib and SN-38 treatment inhibits CD44 expression by promoting its lysosomal degradation in HNSCC cells. However, it is still unclear whether inhibition of CD44 expression in HNSCC cells can directly suppress tumor regrowth after therapy. Thus, it may be necessary to elucidate the relationship between the effects of these chemotherapeutic agents on CD44 expression and tumor recurrence/metastasis in future studies.
Databáze: OpenAIRE
Externí odkaz: