RESUMO
Multidrug resistance (MDR) is a major clinical obstacle in the successful treatment of patients with metastatic nasopharyngeal carcinoma (NPC). Results from previous studies suggest that microRNAs (miRNA) may be involved in promoting MDR in multiple cancer types. However, the role of miR125b in modulating the MDR of NPC is elusive. In the present study, miR125b expression in cisplatin (DDP) resistant CNE2 cells (CNE2/DDP) was compared with parental counterparts, using reverse transcriptionquantitative polymerase chain reaction. A >3fold reduction in miR125b expression levels was observed in CNE2/DDP cells compared with parental CNE2 cells. Ectopic expression of miR125b by transfecting CNE2/DDP cells with miR-125b mimics, increased DDPinduced cytotoxicity, apoptosis and chemosensitivity. By contrast, suppression of miR-125b by transfecting CNE2 cells with miR125b inhibitors, reduced DDPinduced cytotoxicity and apoptosis, and facilitated cisplatin resistance. The results suggest that miR125b may regulate the sensitivity of NPC cells to DDP by modulating the expression levels of antiapoptotic factor B-cell CLL/lymphoma 2. Collectively, the results of the present study highlight miR125b as a potential therapeutic target for reversing MDR in NPC.
Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , MicroRNAs/genética , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Carcinoma , Linhagem Celular Tumoral , Resistência a Múltiplos Medicamentos , Regulação Neoplásica da Expressão Gênica , Humanos , Carcinoma Nasofaríngeo , Nasofaringe/efeitos dos fármacos , Nasofaringe/metabolismoRESUMO
OBJECTIVES/HYPOTHESIS: The KiSS-1 gene has been reported to serve as a metastasis suppressor gene in various human malignancies. However, no information is available regarding the role of the KiSS-1 gene or its gene product kisspeptin in nasopharyngeal carcinoma. STUDY DESIGN: Retrospective study. METHODS: Kisspeptin and its receptor AXOR12 expression were assessed using immunohistochemistry in paraffin-embedded tumor tissues from 140 patients diagnosed with nasopharyngeal carcinoma. Immunoreactivity was quantified, and its relationships with patients' clinical parameters and survival were analyzed. RESULTS: Using a 50% cutoff level, the immunoreactivities of kisspeptin and AXOR12 were divided into low and high expression. The expression levels of kisspeptin and AXOR12 in nasopharyngeal carcinoma were well correlated with each other (rs = 19.31, P < 0.01). Low expression of kisspeptin in nasopharyngeal carcinoma was correlated with clinical stage (P = 0.01), N stage (P = 0.03), and metastasis (P = 0.02). Patients with low kisspeptin expression had poorer distant metastasis-free survival than those with high kisspeptin expression (75.32% vs. 83.79%, P = 0.02). Although neither kisspeptin nor AXOR12 were found to be prognostic factors for overall survival, kisspeptin was determined to be an independent prognostic factor for distant metastasis-free survival (P = 0.03) using multivariate analysis. CONCLUSION: In this study, we report for the first time that low kisspeptin expression in nasopharyngeal carcinoma is correlated with poor clinical outcome; kisspeptin could serve as an independent prognostic marker for metastasis in nasopharyngeal carcinoma.
Assuntos
Kisspeptinas/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Adulto , Idoso , Carcinoma , Feminino , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patologia , Estadiamento de Neoplasias , Prognóstico , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Kisspeptina-1 , Estudos RetrospectivosRESUMO
The aim of this study was to explore the effects of erlotinib combined with radiation on human nasopharyngeal carcinoma (NPC) radiosensitivity using the CNE1 and CNE2 cell lines. Human NPC cells were treated with erlotinib and/or radiation. The effect of erlotinib on the radiosensitivity of the cells was detected using a clonogenic cell survival assay. The rate of apoptosis and the cell cycle were evaluated using flow cytometry. An NPC xenograft model in NOD-SCID mice was used to evaluate the efficacy of the combination therapy of erlotinib with radiation. Erlotinib enhanced the sensitivity of the CNE1 and CNE2 cells to radiation, with sensitization enhancement ratios (SERs) of 1.076 and 1.109, respectively. Erlotinib combined with radiation induced G2/M phase cell cycle arrest in the two cell lines. The mouse tumor model demonstrated a significant reduction in NPC tumor volume in mice treated with erlotinib in combination with radiation when compared with that in mice treated with radiation alone. Erlotinib combined with radiation provoked G2-M phase cell cycle arrest, thereby enhancing the sensitivity of the NPC cells to radiation.
RESUMO
OBJECTIVE: To investigate the correlation of prolactin receptor (PRL-R) expression to estrogen receptor (ER) and progesterone receptor (PR) expressions in primary breast cancer. METHODS: For 130 female patients with breast cancer (median age 46 years), PRL-R expression in the primary tumor was detected by immunohistochemistry, and the correlation between PRL-R and ER/PR expressions was analyzed statistically. RESULTS: PRL-R positivity in the primary tumor was found in 89 of the patients (68.5%), and the positivity rate for PRL-R was positively correlated to ER expression (P<0.05). Further stratification of the patients according to the CerbB-2 status revealed such a correlation only in CerbB-2-positive patients (P<0.05). In the patient cohort, no significant correlation was found in the positivity rate between PRL-R and PR expressions (P>0.05), but in CerbB-2-positive patients, the positivity rate of PRL-R showed a positive correlation to PR expression (P<0.05). CONCLUSION: The positive correlations in positivity rate between the PRL-R and ER/PR expressions are found only in CerbB-2 positive patients with breast cancer, and the expressional status of CerbB-2 affects the correlation between PRL-R and ER/PR expression in breast cancer.