OBJECTIVE: To study the influence of PD173074 on proliferation and apoptosis of nasopharyngeal carcinoma. METHOD: With immunoblotting and RT-PCR, FGFR1 expression was detected in CNE, PONE1 and C666-1 cell lines. With MTT assay,the time-effect and dose-effect correlation between PD173074 and inhibition of CNE proliferation was evaluated. After PD173074 stimulation, the phosphorylation level of FGFR1 and AKT was detected with immunoblotting assay. Furthermore, influence of PD173074 on the activation of Caspase3 and Caspase9 was detected to study the underlying mechanism of why PD173074 could inhibit CNE proliferation. RESULT: FGFR1 has the highest expression in CNE cell line. Under incubation of 10 nmol/L PD173074 stimulation for 36 hours to 72 hours, the phosphorylation of FGFR1 and AKT was impaired significantly, which further reduced the proliferation of CNE. Moreover, PD173074 can activate the intrinsic apoptotic pathway by stimulating Caspase9,which activated Caspase3 and induced the apoptosis. CONCLUSION PD173074 could inhibit proliferation of nasopharyngeal carcinoma cell through reducing the phosphorylation of FGFR1 and AKT. Additionally, PD173074 can induce CNE apoptosis by activating intrinsic apoptotic pathway via cleaving Caspase9 and Caspase3.
Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Carcinoma ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; drug therapy ; pathology ; Pyrimidines ; pharmacology

OBJECTIVE: To study the expression of excision repair cross-complementing 1 (ERCC1) and the treatment of cisplatin-based chemotherapy in local advanced nasopharyngeal carcinoma (NPC). METHOD: The expression of ERCC1 protein in 107 cases with NPC and in 48 normal nasopharyngeal tissues adjacent to the cancer was detected by immunohistochemical method. RESULT: High expression of ERCC1 was observed in 52 cases with NPC, and 18 cases normal nasopharyngeal tissues, there was no statistically significant differences between them. The expression of ERCC1 protein was significant correlated with patient total TNM stage, but not significantly correlated with age, gender, histological type, T stage and N stage. The recent treatment efficiency in Low ER-CCl expression cases was higher than high expression cases. There was statistically significant difference between them. In 97 follow-up cases, 2 cases died, 5 cases with liver and lung metastasis, there was no statistically significant difference between them. CONCLUSION ERCC1 expression maybe regarded as indicator platinum based chemotherapy sensitivity prediction in nasopharyngeal carcinoma, and also helpful for formulating individualized treatment. The immunohistochemical detection is also simple and effective detection method for ERCC1 expression.
Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma ; Cisplatin ; therapeutic use ; DNA-Binding Proteins ; biosynthesis ; Endonucleases ; biosynthesis ; Humans ; Lung Neoplasms ; secondary ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; drug therapy ; metabolism ; pathology

The transwell chamber migration assay and the patch-clamp technique were used to investigate the volume-activated Cl(-) current (I(Cl.vol)) in migrated nasopharyngeal carcinoma cells (CNE-2Z). 47% hypotonic solution activated a ICl.vol in the migrated CNE-2Z cells. Compared with the control cells (non-migrated), the properties of this current and the sensitivity to Cl(-) channel blockers were changed. The current density in migrated CNE-2Z cells was higher than that in non-migrated cells. The current was almost completely inhibited by extracellular application of adenosine-5'-triphosphate (ATP, 10 mmol/L), 5-nitro-2-3-phenylpropylamino benzoic acid (NPPB, 100 mmol/L) and tamoxifen (30 mmol/L) in all voltage steps applied. The inhibition of NPPB and tamoxifen on the current was stronger in migrated cells than that in non-migrated cells. The permeability sequence of the four anions was Br(-)>Cl(-)> I (-)>Gluconate. The sequence was different from that of the non-migrated cells (I(-)> Br(-)> Cl(-)> Gluconate). The results suggest that volume-activated chloride channels may be involved in the CNE-2Z cell migration.
Carcinoma ; drug therapy ; metabolism ; pathology ; Cell Cycle ; drug effects ; physiology ; Cell Division ; drug effects ; Cell Movement ; drug effects ; Cell Size ; drug effects ; Chloride Channels ; antagonists & inhibitors ; metabolism ; physiology ; Chlorides ; metabolism ; Humans ; Nasopharyngeal Neoplasms ; drug therapy ; metabolism ; pathology ; Nitrobenzoates ; pharmacology ; Patch-Clamp Techniques ; Tamoxifen ; pharmacology ; Tumor Cells, Cultured

OBJECTIVE: This study was designed to evaluate the effect of zhongjiefeng extracts on telomerase activity and apoptosis of implanted human nasopharyngeal carcinoma cell lines in nude mice. METHOD: Nude mice with implanted human nasopharyngeal carcinoma cell lines CNE1 and CNE2 were randomly divided into three groups, which were the group of zhong-jiefeng, normal control group, and CTX therapy group. The weight of nude mice and the volume of tumor were regularly measured. After a course of treatment (30 d), tumor tissues were obtained with autopsy, and then they were weighed to calculate the inhibitive rate of the growth of tumor. The changes of ultra micro-structure of NPC cells were observed by transmission electron microscope. Expressions of Bcl-2 and Bax of xenografts were investigated by immunohistochemistry. The apoptosis of CNE1 and CNE2 cells was observed using TUNEL and FACS with PI-staining. The telomerase activity was observed by TRAP-ELISA method. RESULT: The zhongjiefeng extracts significantly inhibit the growth of tumor compared to normal control group. The inhibitory rate were 40.8% (P < 0.01) and 46.8% (P < 0.01), respectively. The expression of Bcl-2 was lower (P < 0.01) and the expression of Bax was higher (P < 0.01) in the zhongjiefeng group than that in normal control group. Electron microscopy indicated the typical apoptosis of tumor cells, such as marginal nuclei, chromatin condensation and nuclei fragmentation, and apoptotic bodies. As result of the flow cytometry showed, the exhibition rate of apoptosis of cell in the group treated with zhongjiefeng was higher than that of normal control group (P < 0.01) in G0/G1 phase. Zhongjiefeng arrested cells in G0/G1 phase of the cell cycle. The telomerase activity of zhongjiefeng and CTX group was lower than that of the normal group (P < 0.01). CONCLUSION Zhongjie feng suppressed the growth of tumor in vivo. The anticancer effects of zhongjiefeng were associated with the induction of apoptosis and partly with the suppression of telomerase activity.
Animals ; Apoptosis ; drug effects ; Cell Line, Tumor ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Nasopharyngeal Neoplasms ; drug therapy ; metabolism ; pathology ; Neoplasm Transplantation ; Telomerase ; metabolism ; Xenograft Model Antitumor Assays

The prognostic value of T category for locoregional control in patients with nasopharyngeal carcinoma (NPC) has decreased with the extensive use of intensity-modulated radiotherapy (IMRT). We aimed to develop a prognostic scoring system (PSS) that incorporated tumor extension and clinical characteristics for locoregional control in NPC patients treated with IMRT. The magnetic resonance imaging scans and medical records of 717 patients with nonmetastatic NPC treated with IMRT at Sun Yat-sen University Cancer Center between January 2003 and January 2008 were reviewed. Age, pathologic classification, primary tumor extension, primary gross tumor volume (GTV-p), T and N categories, and baseline lactate dehydrogenase (LDH) level were analyzed. Hierarchical cluster analysis as well as univariate and multivariate analyses were used to develop the PSS. Independent prognostic factors for locoregional relapse included N2-3 stage, GTV-p ≥26.8 mL, and involvement of one or more structures within cluster 3. We calculated a risk score derived from the regression coefficient of each factor and classified patients into four groups: low risk (score 0), intermediate risk (score >0 and ≤1), high risk (score >1 and ≤2), and extremely high risk (score >2). The 5-year locoregional control rates for these groups were 97.4%, 93.6%, 85.2%, and 78.6%, respectively (P < 0.001). We have developed a PSS that can help identify NPC patients who are at high risk for locoregional relapse and can guide individualized treatments for NPC patients.
Adolescent ; Adult ; Aged ; Carcinoma ; Carcinoma, Squamous Cell ; diagnosis ; drug therapy ; metabolism ; pathology ; radiotherapy ; Chemoradiotherapy ; Female ; Humans ; Kaplan-Meier Estimate ; L-Lactate Dehydrogenase ; metabolism ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; diagnosis ; drug therapy ; metabolism ; pathology ; radiotherapy ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Radiotherapy Dosage ; Radiotherapy, Intensity-Modulated ; methods ; Risk Assessment ; methods ; Tumor Burden ; Young Adult

Gemcitabine has high activity against nasopharyngeal carcinoma (NPC). The level of ribonucleotide reductase subunit M1 (RRM1) expression is closely related to the efficacy of gemcitabine on non-small cell lung cancer and pancreatic cancer. However, the expression of RRM1 and its association with sensitivity to gemcitabine-based chemotherapy in advanced NPC is not known. In this study, we retrospectively collected 48 formalin-fixed, paraffin-embedded NPC tissues to evaluate the expression of RRM1 using immunohistochemistry. All patients were diagnosed and treated with gemcitabine-based chemotherapy at Sun Yat-sen University Cancer Center. RRM1 expression was positive in 17(35%) patients. RRM1 expression was not associated with sex, age, performance status, WHO histological type, number of distant metastases, previous treatment, or cycles of gemcitabine-based chemotherapy(P> 0.05). The progression-free survival of the RRM1-positive group was shorter than that of the RRM1-negative group (5 months vs. 7 months, P = 0.036), and the response rate of the RRM1-positive group was somewhat lower than that of the RRM1-negative group (51.6% vs. 35.3%, P = 0.278). There was no significant difference in median survival between the RRM1-positive and RRM1-negative groups (22 months vs. 19 months, P = 0.540). Our results show that RRM1-negative expression is related with longer progression-free survival in advanced NPC patients treated with gemcitabine-based regimens.
Adult ; Aged ; Antimetabolites, Antineoplastic ; therapeutic use ; Deoxycytidine ; analogs & derivatives ; therapeutic use ; Disease-Free Survival ; Drug Resistance, Neoplasm ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; drug therapy ; metabolism ; pathology ; Neoplasm Staging ; Remission Induction ; Retrospective Studies ; Survival Rate ; Tumor Suppressor Proteins ; metabolism

PURPOSE: Tolfenamic acid (TA), a non-steroidal anti-inflammatory drug, is known to exhibit antitumor effects in various cancers apart from nasopharyngeal cancer (NPC). NPC exhibits high invasiveness, as well as metastatic potential, and patients continue to suffer from residual, recurrent, or metastatic disease even after chemoradiation therapy. Therefore, new treatment strategies are needed for NPC. In this study, we investigated the efficacy and molecular mechanisms of TA in NPC treatment. MATERIALS AND METHODS: TA-induced cell death was detected by cell viability assay in the NPC cell lines, HNE1 and HONE1. Wound healing assay, invasion assay, and Western blot analysis were used to evaluate the antitumor effects of TA in NPC cell lines. RESULTS: Treatment with TA suppressed the migration and invasion of HNE1 and HONE1 cells. Hepatocyte growth factor enhanced the proliferation, migration, and invasion abilities of NPC cells. This enhancement was successfully inhibited by TA treatment. Treatment with TA increased phosphorylation of p38, and the inhibition of p38 with SB203580 reversed the cytotoxic, anti-invasive, and anti-migratory effects of TA treatment in NPC cell lines. Moreover, inhibition of p38 also reversed the decrease in expression of Slug that was induced by TA treatment. CONCLUSION: In conclusion, the activation of p38 plays a role in mediating TA-induced cytotoxicity and inhibition of invasion and migration via down-regulation of Slug.
Animals ; Anti-Inflammatory Agents, Non-Steroidal/*pharmacology/therapeutic use ; Cell Line, Tumor ; Cell Movement/*drug effects ; Cell Proliferation/*drug effects ; Cell Survival/*drug effects ; Down-Regulation ; Gastropoda ; Gene Expression Regulation, Neoplastic/drug effects ; Hepatocyte Growth Factor/metabolism/*pharmacology ; Humans ; Imidazoles ; MAP Kinase Signaling System/drug effects ; Nasopharyngeal Neoplasms/*drug therapy/metabolism/pathology ; Neoplasm Invasiveness/*prevention & control ; Phosphorylation/drug effects ; Pyridines ; ortho-Aminobenzoates/*pharmacology/therapeutic use