Related Experiment Videos
Multidrug resistance gene 1 expression in salivary gland adenocarcinomas and oral squamous-cell carcinomas
T Uematsu1, T Hasegawa, B Y Hiraoka
1Department of Oral and Maxillofacial Surgery, Matsumoto Dental University School of Dentistry, Shiojiri, Nagano 399-0781, Japan.
Abstract:
In combined chemotherapy for head-and-neck cancer (HNC), salivary gland-cell adenocarcinoma (SGA) shows insufficient clinical outcome, and it has been suggested that the sensitivity and/or the mechanism of resistance to anti-cancer drugs are different between SGA and oral squamous-cell carcinoma (SCC). The aim of our study was to clarify whether P-glycoprotein (P-gp) expression is associated with multidrug resistance (MDR) in HNC and the difference in the process of its development between SGA and SCC. In immunohistochemical analysis, P-gp expression was found in the ductal cells of salivary glands but not in oral mucosal epithelium. In cancer tissues, a few SCC cells in 12 of 37 and most cells in all SGAs expressed P-gp. The intensive P-gp expression was significantly found in SGA compared with SCC. In an in vivo chemotherapeutic model using tumor-bearing nude mice, P-gp expression in counterparts was observed in only a few cells of the HSY line, while no P-gp expression was observed in Hepd cells. However, P-gp expression was developed in both HSY and Hepd cell lines after vincristine (VCR) treatment. RT-PCR showed that the mean ratios of mdr1 mRNA expression levels in HSY clones were 3.7-fold higher than those in Hepd clones after VCR treatment, while each cell line exhibited both induction and activated production of P-gp. These results suggest that P-gp-related MDR in SGA is an inherent phenotype caused by both high levels of P-gp induction and activated P-gp production during VCR treatment, while that in SCC is an acquired phenotype chiefly caused by induction of P-gp.
Insights
Salivary gland adenocarcinoma (SGA) exhibits inherent multidrug resistance (MDR) due to P-glycoprotein (P-gp) induction and production. Oral squamous cell carcinoma (SCC) develops MDR primarily through P-gp induction, impacting head-and-neck cancer chemotherapy outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Salivary gland adenocarcinoma (SGA) shows poor outcomes in head-and-neck cancer (HNC) chemotherapy.
- P-glycoprotein (P-gp) mediated multidrug resistance (MDR) is a potential factor differentiating drug sensitivity between SGA and oral squamous cell carcinoma (SCC).
Purpose of the Study:
- To investigate the association between P-gp expression and MDR in HNC.
- To elucidate the distinct mechanisms of P-gp development in SGA versus SCC.
Main Methods:
- Immunohistochemical analysis of P-gp expression in normal salivary glands, oral mucosa, and HNC tissues.
- In vivo chemotherapeutic models using tumor-bearing nude mice.
- RT-PCR to assess mdr1 mRNA expression levels in cell lines after vincristine (VCR) treatment.
Main Results:
- P-gp was expressed in salivary gland ductal cells but not oral epithelium; intensive P-gp expression was observed in SGA compared to SCC.
- In vivo models showed P-gp expression developed in both HSY (SGA) and Hepd (SCC) cell lines after VCR treatment.
- RT-PCR revealed significantly higher mdr1 mRNA levels in VCR-treated HSY clones compared to Hepd clones, indicating differential P-gp induction and production.
Conclusions:
- P-gp-related MDR in SGA is an inherent phenotype, driven by high P-gp induction and activated production during chemotherapy.
- P-gp-related MDR in SCC is primarily an acquired phenotype, mainly resulting from P-gp induction.
- Understanding these differential mechanisms is crucial for improving HNC treatment strategies.