BACKGROUND AND OBJECTIVEThe expression levels of glucose-regulated protein 78 (GRP78) were elevated and correlated with resistance to chemotherapy drug VP-16 in lung cancer cells. However, little is known about the relationship between its expression and resistance to cisplatin in lung cancer cells. The aim of this study was to investigate the expression of GRP78 under the induction of A23187 and its significance in the resistance to anti-tumor drugs cisplatin in a human lung cancer SPCA-1 cell line.

METHODSRT-PCR and Western blot were used to analyze the expression of GRP78 at mRNA and protein levels in SPCA-1 cell line induced byA23187 at different concentrations (0, 1, 2, 4, 6 microM). MTT was used to determine the effect of cisplation on cell survival.

RESULTSThe expressions of GRP78 at both mRNA and protein levels were increased obviously in SPCA-1 cell line induced by A23187, with a manner of dose-dependent of A23187 to a great degree; MTT assay showed that the cell survival rate of the A23187-induced group decreased significantly compare to the control group, also with a concentration-dependent manner of A23187.

CONCLUSIONThe expression of GRP78 at both mRNA and protein levels were increased obviously in SPCA-1 cell line induced by A23187. The enhancement of GRP78 showed a negative correlation with the cell survival rate treated by cisplatin. All these indicated that overexpression of GRP78 can enhance the sensitivity to cisplatin and there is correlation between the expression of GRP78 and resistance to cisplatin of human lung cancer SPCA-1 cell line.

Antineoplastic Agents ; pharmacology ; Blotting, Western ; Calcimycin ; pharmacology ; Cell Line, Tumor ; Cell Survival ; drug effects ; Cisplatin ; pharmacology ; Drug Resistance, Neoplasm ; genetics ; physiology ; Heat-Shock Proteins ; genetics ; metabolism ; Humans ; Reverse Transcriptase Polymerase Chain Reaction

Objective:To analyze the factors affecting olfactory disfunctions in patients with chronic rhinosinusitis with nasal polyps (CRSwNP).Methods:This was a retrospective analysis. Eighty-eight patients with CRSwNP who underwent endoscopic sinus surgery in Beijing Anzhen Hospital from 2014 to 2018 were enrolled, including 22 males and 66 females, with the age of (48.1±11.3) years old(Mean±SD). Sniffin′ Sticks olfactory test, Lund-Mackay score and modified sinus CT olfactory cleft score, nasal resistance and acoustic reflex examination, blood routine and blood biochemistry test, serum specific IgE test were performed before surgery and nasal polyps of all patients were collected for eosinophil count during surgery. According to bilateral total TDI score, the patients were divided into normal olfactory function group and olfactory disfunction group. The clinical baseline data were compared between the two groups. According to the results of single factor analysis, factors which were significant different between the two groups and clinically useful indicators were further included in the multivariate Logistic regression model analysis, then a model predicting olfactory disfunction in patients with CRSwNP was initially established. P<0.05 was considered statistically significant. Results:Among 88 patients with CRSwNP, 32 (36.4%) patients were with normal olfaction and 56 (63.6%) patients were with olfactory disfunction, including 40 (45.5%) of hyposmia and 16 (18.2%) of anosmia. Tissue eosinophil count, blood eosinophil percentage and blood urea concentration had significant difference between the two groups (12.7[2.0, 52.3]/HP ( M[ P25, P75]) vs 38.6[16.2, 87.0]/HP, 2.75[1.60, 4.80]% vs 4.35[2.50, 6.60]%, (5.56±1.15) mmol/L vs (4.98±1.33) mmol/L, all P<0.05). Modified sinus CT olfactory cleft score and Lund-Mackay score except for ostiomeatal complex score were statistically significant between the two groups (all P<0.05). Multivariate Logistic regression analysis showed that the bilateral and total olfactory cleft score and blood urea concentration were statistically significant, in addition, the bilateral and total olfactory cleft score was a risk factor ( OR=2.108, 95 %CI: 1.407-3.159, P<0.001) and blood urea within a certain concentration was a protective factor ( OR=0.461, 95 %CI: 0.240-0.884, P=0.020). Further studies found that the area under the ROC curve of the model with tissue eosinophil count, blood eosinophil percentage, bilateral and total olfactory cleft score, total inspiratory volume and blood urea concentration was 0.888 ( P<0.01), which had good predictive value for olfactory disorders in CRSwNP. Conclusions:The modified sinus CT olfactory cleft score is closely related to the olfactory disorders in patients with CRSwNP. A certain degree of elevated blood urea concentration may have a protective effect on the olfactory function of patients with CRSwNP.

Nasopharyngeal carcinoma (NPC) is a malignant tumor that mainly occurs in East and Southeast Asia. Although patients benefit from the main NPC treatments (e.g., radiotherapy and concurrent chemotherapy), persistent and recurrent diseases still occur in some NPC patients. Therefore, investigating the pathogenesis of NPC is of great clinical significance. In the present study, replication factor c subunit 4 (RFC4) is a key potential target involved in NPC progression via bioinformatics analysis. Furthermore, the expression and mechanism of RFC4 in NPC were investigated in vitro and in vivo. Our results revealed that RFC4 was more elevated in NPC tumor tissues than in normal tissues. RFC4 knockdown induced G2/M cell cycle arrest and inhibited NPC cell proliferation in vitro and in vivo. Interestingly, HOXA10 was confirmed as a downstream target of RFC4, and the overexpression of HOXA10 attenuated the silencing of RFC4-induced cell proliferation, colony formation inhibition, and cell cycle arrest. For the first time, this study reveals that RFC4 is required for NPC cell proliferation and may play a pivotal role in NPC tumorigenesis.
Humans ; Nasopharyngeal Carcinoma/pathology* ; Carcinoma/pathology* ; Replication Protein C/metabolism* ; Nasopharyngeal Neoplasms/pathology* ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Cell Movement