Yandong Nan

Phloretin exhibits an anticancer effect and enhances the anticancer ability of cisplatin on non-small cell lung cancer cell lines by regulating expression of apoptotic pathways and matrix metalloproteinases

Non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancer cases and the prognosis of NSCLC patients is unsatisfactory since 5-year survival rate of NSCLC is still as low as 11%. Natural compounds derived from plants with few or no side effects have been recognized as alternative or auxiliary cure for cancer patients. Phloretin is such an agent possessing various pharmacological activities; however, there is scarce information on its anticancer effects on NSCLC. It was evaluated and confirmed, in the present study, that phloretin inhibited proliferation and induced apoptosis in A549, Calu-1, H838 and H520 cells in a dose-dependent manner, phloretin also suppressed the invasion and migration of NSCLC cells. We further confirmed that phloretin dose-dependently suppressed the expression of Bcl-2, increased the protein expression of cleaved-caspase-3 and -9, and deregulated the expression of matrix metalloproteinases (MMP)-2 and -9 on gene and protein levels. Besides, evaluations revealed that phloretin enhanced the anticancer effects of cisplatin on inhibition of proliferation and induction of apoptosis in NSCLC cells. Moreover, phloretin facilitated the effects of cisplatin on deregulation of Bcl-2, MMP-2 and -9, and upregulation of cleaved-caspase-3 and -9. In conclusion, the present study demonstrated that phloretin possessed anticancer effects and enhanced the anticancer effects of cisplatin on NSCLC cell lines by suppressing proliferation, inducing apoptosis and inhibiting invasion and migration of the cells through regulating apoptotic pathways and MMPs.

3,5,4′-tri-O-acetylresveratrol Ameliorates Seawater Exposure-Induced Lung Injury by Upregulating Connexin 43 Expression in Lung

The aim of the present study was to examine the effects of 3,5,4′-tri-O-acetylresveratrol on connexin 43 (Cx43) in acute lung injury (ALI) in rats induced by tracheal instillation of artificial seawater. Different doses (50, 150, and 450 mg/kg) of 3,5,4′-tri-O-acetylresveratrol were administered orally for 7 days before modeling. Four hours after seawater inhalation, histological changes, contents of TNF-α, IL-1β and IL-10, and the expression of Cx43 in lungs were detected. Besides, the gap junction communication in A549 cells and human umbilical vein endothelial cells (HUVECs) challenged by seawater was also evaluated. Histological changes, increased contents of inflammatory factors, upregulation in gene level, and deregulation in protein level of Cx43 in lungs stimulated by seawater were observed. On the other hand, pretreatment with 3,5,4′-tri-O-acetylresveratrol significantly inhibited infiltration of inflammation, development of pulmonary edema, and contents of inflammatory mediators in lungs. Above all, 3,5,4′-tri-O-acetylresveratrol upregulated the expression of Cx43 in both gene and protein levels, and its intermediate metabolite, resveratrol, also enhanced the gap junction communication in the two cell lines. The results of the present study suggested that administration of 3,5,4′-tri-O-acetylresveratrol may be beneficial for treatment of inflammatorycellsin lung.

Resveratrol enhanced anticancer effects of cisplatin on non-small cell lung cancer cell lines by inducing mitochondrial dysfunction and cell apoptosis

Resveratrol is a plant-derived natural compound which possesses potential anticancer properties. However, there are scarce reports on its anticancer effects in non-small cell lung cancer and its auxiliary function on the anticancer effects of cisplatin. In the present study, we investigated the effects of resveratrol on the cell viability and apoptosis in human non-small cell lung cancer H838 and H520 cell lines. It has been found that resveratrol inhibited the proliferation of H838 and H520 cells in a dose- and time-dependent manner, and apoptosis was increased in cells treated with resveratrol which was associated with the depolarization of mitochondrial membrane potential, release of cytochrome c from mitochondria to cytosol, and abnormal expression of Bcl-2 and Bax proteins. Above all, resveratrol enhanced the effects of cisplatin on inhibition of cancer cell proliferation, induction of cell apoptosis, depolarization of mitochondrial membrane potential, release of cytochrome c and regulation on expression of Bcl-2 and Bax. Results from the present study demonstrated that resveratrol exhibited its anticancer effects on non-small cell lung cancer H838 and H520 cell lines, and enhanced the antitumor effects of cisplatin by regulating the mitochondrial apoptotic pathway. These results have put forward the rationale for further basic research and preclinical investigation on the anticancer effects of resveratrol against human non-small cell lung cancer.

17β-Estradiol administration attenuates seawater aspiration-induced acute lung injury in rats

There is very little evidence on the value of administering estrogen in cases of seawater drowning which can induce acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Therefore, this study aimed to investigate whether 17β-estradiol (E2) treatment can attenuate seawater aspiration-induced ALI in rats. In the experiment, ALI was induced by endotracheal instillation of seawater (4mL/kg) and the rats were then given intraperitoneal injection of E2 (5mg/kg) 20min after seawater instillation. Finally, the changes of arterial blood gases which contained hydrogen ion concentration (pH), arterial oxygen tension (PaO(2)) and arterial carbon dioxide tension (PaCO(2)) were measured and the measurement of extravascular lung water (EVLW) was observed. The pulmonary histological changes were evaluated by hematoxylin-eosin stain. The expression of aquaporins (AQPs) 1, AQP5, and estrogen receptor-β (ERβ) was measured by western blotting and immunohistochemical methods. The results showed that compared with normal saline water, seawater aspiration induced more serious ALI in rats which was markedly alleviated by E2 treatment. Meanwhile, the ERβ in lung tissues was activated after E2 administration. The seawater aspiration group also presented with severe pulmonary edema which was paralleled with over expressed AQP1 and AQP5. However, the up-regulation of AQP1 and AQP5 was suppressed by the administration of E2, resulting in an attenuation of lung edema. In conclusion, E2 treatment could effectively attenuate seawater aspiration-induced acute lung injury in rats by the down-regulation of AQP1 and AQP5.

Therapeutic effects of sequential therapy by electric coagulation, cryotherapy and balloon dilation with an electronic video bronchoscope

The aim of the current study was to retrospectively analyze clinical data concerning bronchostenosis or bronchial obstruction caused by endobronchial tuberculosis. Fifty-six cases were subjected to bronchoscopy and chest computed tomography to assess the prognosis of bronchostenosis and bronchial obstruction. Based on reliable and effective anti-pulmonary tuberculosis therapy, these conditions were treated sequentially by electric coagulation, cryotherapy and balloon dilation with an electronic video bronchoscope during outpatient consultation or inpatient hospitalization. Fifty-three subjects with bronchostenosis recovered to varying degrees, a recovery rate of 94.6%. Thirteen of the 15 cases with bronchial obstruction reopened (86.7%). The clinical symptoms of these cases appeared to be in remission. Bronchostenosis or bronchial obstruction resulting from endobronchial tuberculosis may be treated by electric coagulation, cryotherapy and balloon dilation with an electronic video bronchoscope.

Analysis of novel microRNA targets in drug-sensitive and -insensitive small cell lung cancer cell lines

Advances in chemotherapy have failed to improve the long-term survival rate of small cell lung cancer (SCLC) patients due to multidrug resistance (MDR). The mechanisms of MDR are complex involving multiple genes and a variety of mechanisms. MicroRNAs (miRNAs) are non-coding RNAs theoretically involved in gene regulation. The aim of the present study was to explore the role of miRNAs in SCLC occurrence and multidrug resistance. Expression levels of known miRNAs in SCLC cell line H446 and its multidrug-resistant cell line H446/CDDP were analyzed using the next generation high through-put Illumina Solexa sequencing technology, and expression of a group of specific miRNAs was validated by quantitative polymerase chain reaction (qPCR). Furthermore, novel miRNAs and their putative target genes in the two SCLC cell lines were predicted with the help of software developed by Beijing Genomics Institute and analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The results revealed a set of known miRNAs with altered expression in the H446 and H446/CDDP cells which may be associated with multidrug resistance of SCLC. Biological information analysis of the novel miRNAs and their putative target genes further elucidated the role of miRNAs in MDR. In addition, the pathway prediction by KEGG analysis may provide clues for further research on MDR of SCLC.

Discovery of a set of biomarkers of human lung adenocarcinoma through cell-map proteomics and bioinformatics

Carcinogenesis of lung adenocarcinoma remains unclear and very few biomarkers have been accepted for routine clinical use. In order to explore the pathogenesis and screen ideal biomarkers, we conducted cell-map proteomics study in human lung adenocarcinoma. Homogeneous lung adenocarcinoma cells were purified by laser capture microdissection (LCM). A high performance liquid chromatography (HPLC) system was used to separate the total solution proteins. The resulting MS/MS spectra were automatically searched for proteins against IPI human protein database using the TurboSEQUEST searching engine. Physico-chemical properties of the identified proteins, including molecular weight (MW), isoelectric point (PI), were described based on various proteomics web server and statistical analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were used to analyze function of expressed proteins and screen candidate biomarkers according to biological annotation. A total of 843 distinct proteins were identified and were categorized as 10 sorts of molecular function and 17 sorts of biological process based on GO annotation. Further searching against KEGG pathways found that six proteins were involved in WNT signaling pathway, apoptosis pathway, Erb-2 signaling pathway, p53 signaling pathway, ubiquitin-mediated proteolysis and were might be hopefully screened as candidate markers of lung adenocarcinoma. The present study through LCM and cell-map proteomics showed a full view on the expressed protein profiles of lung adenocarcinoma. Several candidate markers are hopeful to be used as molecular targets of diagnosis, treatment and prognosis of lung adenocarcinoma.