RESUMO
We examined the effect of E-cadherin expression on epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) molecular targeted therapy sensitivity/resistance. We treated MCF-7, MDA-MB-231, T24, SiHa, H460, SK-HEP-1, MHCC97-H, and THP-1 cells with the EGFR-TKIs PD153035 and gefitinib, and then tested the drug-resistance and sensitivity using the MTT method, calculated IC50 values for each cell line, and compared the results to E-cadherin content. The MTT assay was used to determine the survival rates of MCF-7, MDA-MB-231, T24, SiHa, H460, SK-HEP-1, MHCC97-H, and THP-1 cells upon the action of EGFR-TKI (PD153035, gefitinib). For PD153035, the IC50 in MCF-7, MDA-MB-231, T24, and SiHa cells differed from that of H460, SK-HEP-1, MHCC97-H, and THP-1 (P < 0.05). Following gefitinib treatment, the IC50 values of MCF-7, MDA-MB-231, T24, and SiHa cells differed from those of H460, SK-HEP-1, MHCC97-H, and THP-1 cells (P < 0.01). The survival rate of MCF-7, MDA-MB-231, T24, and SiHa cells clearly decreased with increasing drug concentration, indicating the cells were sensitive to the drugs and that E-cadherin expression was positive; however, H460, SK-HEP-1, MHCC97-H, and THP-1 cells showed no significant decreased with increasing drug concentration, indicating that they were resistant to the drugs and that E-cadherin expression was negative. The survival rate of epithelial tumor cells through the action of EGFR-TKI is related to E-cadherin expression. E-cadherin may play a significant role in the sensitivity regulation of EGFR molecular targeting treatment. E-cadherin may provide important clues for selecting proper EGFR-TKI molecular targeting treatment.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Caderinas/biossíntese , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias da Mama/patologia , Caderinas/genética , Proliferação de Células/efeitos dos fármacos , Receptores ErbB/antagonistas & inibidores , Gefitinibe , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7 , Terapia de Alvo Molecular , Inibidores de Proteínas Quinases/administração & dosagem , Quinazolinas/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genéticaRESUMO
PURPOSE: T cells are dominant in the immune regulation of malignant pleural effusion (MPE). However, it is unclear about the role of IL-17+ T cells, particularly for IL-17+CD8+ Tc17 cells in antitumor immunity. This retrospective study is aimed at evaluating the prognostic significance of IL-17+ T cells in patients with MPE. METHODS: The frequency of IL-17+CD4+ Th17 and IL-17+CD8+ Tc17 cells in peripheral blood (PB), pleural fluids (PF), and tumor tissues in 24 patients undergoing thoracoscopy was determined by flow cytometry, immunohistochemistry, and ELISA. The association among the different measures was analyzed by Spearman's correlation tests. RESULTS: The percentages of PF Th17 and Tc17 cells were significantly higher than those in the PB of MPE patients and healthy controls (p < 0.01). Analysis of Th17 and Tc17 cells in the tumor tissues indicated that the percentages of Th17 and Tc17 cells in the invading tumor edge were significantly higher than those in the non-tumor tissues and intra-tumor regions (p < 0.05). More importantly, the percentages of IL-17+ T cells were associated with prolonged survival of patients with MPE. CONCLUSIONS: Both Th17 and Tc17 cells were involved in the tumor immunity against MPE. Increased frequency of Tc17 cells may serve as a biomarker for the prognosis of patients with MPE.