RESUMO
BACKGROUND: The determination of sensitive chemotherapy drugs for gastric cancer (GC) is one of the greatest challenges of adjuvant therapy. Here we evaluated the chemosensitivity of GC to anticancer drugs and the telomerase reverse transcriptase (hTERT) mRNA expression, and investigated the relationship of them. METHODS: The GC cells which were collected from 68 patients with primary GC were primary cultured. The chemosensitivity of GC cells to anticancer drugs was evaluated successfully using the MTT assay for 60 cases of GC cells, and the hTERT mRNA expression was examined in 60 cases of GC tissues and corresponding normal gastric mucosa and 6 cases of chronic superficial gastritis mucosa by in situ hybridization. RESULTS: Taxol, cisplatin and 5-fluorouracil were in general more effective than adriamycin and mitomycin for GC cells, and the chemosensitivity to anticancer drugs was associated with tumor histological types and a worse tumor grade. Compared to normal gastric mucosa tissues, hTERT mRNA expression was significantly increased in GC (P<0.05), which was related with a worse differentiation and drug-resistance to 5-fluorouracil or adriamycin in GC. CONCLUSIONS: These data demonstrate for the first time that examinations of hTERT mRNA expression as an important factor could be used to select the chemotherapeutic drugs for GC patients. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1793217009875483.
Assuntos
Adenocarcinoma/genética , Antineoplásicos/farmacologia , Biomarcadores Tumorais/genética , Resistencia a Medicamentos Antineoplásicos/genética , RNA Mensageiro/metabolismo , Neoplasias Gástricas/genética , Telomerase/genética , Adenocarcinoma/enzimologia , Adenocarcinoma/patologia , Adenocarcinoma Mucinoso/enzimologia , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Papilar/enzimologia , Adenocarcinoma Papilar/genética , Adenocarcinoma Papilar/patologia , Carcinoma de Células em Anel de Sinete/enzimologia , Carcinoma de Células em Anel de Sinete/genética , Carcinoma de Células em Anel de Sinete/patologia , Estudos de Casos e Controles , Diferenciação Celular , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Doxorrubicina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Fluoruracila/farmacologia , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Hibridização In Situ , Mitomicina/farmacologia , Gradação de Tumores , Paclitaxel/farmacologia , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/patologia , Células Tumorais CultivadasRESUMO
OBJECTIVE: To evaluate in vitro anti-tumor effect of chemotherapeutic drugs on human gastric cancer cells, and investigate the relationship with Bcl-2 expression. METHODS: Single cell suspension was prepared from fresh gastric cancer tissue and exposed to taxol (Tax), 5-fluorouracil (5-FU), cisplatin (CDDP), adriamycin (ADM), mitomycin (MMC) respectively for 48 hours. Metabolic activity and inhibitory rate of cells were detected by MTT assay. Expression of Bcl-2 was examined with immunohistochemistry. RESULTS: The inhibitory rates of cancer cells exposed to chemotherapeutic drugs were different and Tax, 5-FU, CDDP had remarkably higher rates than ADM and MMC. The lower differentiated gastric cancer cells were more sensitive than the higher ones. Positive expression rate of Bcl-2 was 80% and the positive cells showed resistance to 5-FU, ADM and MMC. CONCLUSIONS: Chemosensitive testing by MTT assay can constitute the prediction for the application of chemotherapeutic drugs individually. Overexpression of Bcl-2 may contribute to multiple drug-resistance of tumors.
Assuntos
Antineoplásicos/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Neoplasias Gástricas/metabolismo , Adulto , Idoso , Antineoplásicos/uso terapêutico , Sobrevivência Celular , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Mitomicina/farmacologia , Mitomicina/uso terapêutico , Mitomicinas/farmacologia , Mitomicinas/uso terapêutico , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Células Tumorais CultivadasRESUMO
OBJECTIVE: To evaluate in vitro antitumor effects of chemotherapeutic drugs, and investgate the relationship with expression of hTERT mRNA in human gastric cancer tissues. METHODS: Fresh samples of gastric cancer obtained from operation room were prepared to single-cell suspension (3 x 10(5) to 5 x 10(5) cells ml(-1)) and were separately exposed to taxol (TAX), cisplatin (CDDP), 5-fluorouracil (5-Fu), adriamycin (ADM), mitomycin (MMC) for 48 hours. Metabolic activity and inhibitory rate of the cells were determined by trypan blue exclusion and MTT assay. Expression of hTERT mRNA was detected by in situ hybridization (ISH). RESULTS: The inhibition rate of cancer cells exposed to chemotherapeutic drugs was different, and that of TAX, CDDP, 5-Fu was significantly higher than that of ADM and MMC. The positive rate of hTERT mRNA expression was 90.0% (54/60) and positive cells showed resistance to 5-Fu and ADM. CONCLUSION: Overexpression of hTERT mRNA may contribute to primary drug-resistance of tumors. Chemosensitivity tests by MTT assay may contribute to prediction of effectness in applying chemotherapeutic drugs and identify drug-resistant cases.
