Sodium Arsenite Inhibits Proliferation and Induces Apoptosis of Human Hepatic Cells / 中国生物化学与分子生物学报

Arsenic is a potent toxic heavy metal found in the environment that can causes health problems, including liver disease in humans and animals. Chronic exposure to arsenic remains an environmental health problem worldwide, affecting hundreds of millions of people. Although the oxidative stress and apoptosis induced by arsenic have been confirmed, the underlying mechanism of apoptosis has not been fully elucidated. The purpose of this study is to investigate whether sodium arsenite (SA)induced liver toxicity is related to the regulation of DNA replication and repair pathways. The results of MTT and microscopy showed that SA has an inhibitory effect on the proliferation of human hepatocytes (L02), and this effect is time and concentration dependent. Flow cytometry detected the effects of different concentrations of SA on L02 cells. Compared with the control group, high concentrations of SA significantly affected the L02 cell cycle. In addition, RNA sequencing results showed that the differentially expressed genes in cells after SA treatment were concentrated in the DNA replication process and repair pathways. The effect of SA treatment on the expression of human RECQ DNA helicase and repair genes was further confirmed by Western blot and real-time quantitative PCR. In vitro study showed that SA treatment inhibited cell proliferation, and induced apoptosis as well as DNA damage and cell cycle arrest of human liver cell L02. Collectively, these results indicate that arsenic poisoning is related to the regulation of DNA replication and repair pathways, which provides insight for understanding the molecular mechanism of arsenic poisoning.

Autophagy Accompanied with Bisdemethoxycurcumin-induced Apoptosis in Non-small Cell Lung Cancer Cells / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the effects of bisdemethoxycurcumin (BDMC) on non-small cell lung cancer (NSCLC) cell line, A549, and the highly metastatic lung cancer 95D cells.</p><p><b>METHODS</b>CCK-8 assay was used to assess the effect of BDMC on cytotoxicity. Flow cytometry was used to evaluate apoptosis. Western blot analysis, electron microscopy, and quantification of GFP-LC3 punctuates were used to test the effect of BDMC on autophagy and apoptosis of lung cancer cells.</p><p><b>RESULTS</b>BDMC inhibited the viability of NSCLC cells, but had no cytotoxic effects on lung small airway epithelial cells (SAECs). The apoptotic cell death induced by BDMC was accompanied with the induction of autophagy in NSCLC cells. Blockage of autophagy by the autophagy inhibitor 3-methyladenine (3-MA) repressed the growth inhibitory effects and induction of apoptosis by BDMC. In addition, BDMC treatment significantly decreased smoothened (SMO) and the transcription factor glioma-associated oncogene 1 (Gli1) expression. Furthermore, depletion of Gli1 by siRNA and cyclopamine (a specific SMO inhibitor) induced autophagy.</p><p><b>CONCLUSION</b>Aberrant activation of Hedgehog (Hh) signaling has been implicated in several human cancers, including lung cancers. The present findings provide direct evidence that BDMC-induced autophagy plays a pro-death role in NSCLC, in part, by inhibiting Hedgehog signaling.</p>

Role of Wnt Inhibitory Factor-1 in Inhibition of Bisdemethoxycurcumin Mediated Epithelial-to-Mesenchymal Transition in Highly Metastatic Lung Cancer 95D Cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Bisdemethoxycurcumin (BDMC) is an active component of curcumin and a chemotherapeutic agent, which has been suggested to inhibit tumor growth, invasion and metastasis in multiple cancers. But its contribution and mechanism of action in invasion and metastasis of non-small cell lung cancer (NSCLC) are not very clear. Therefore, we tried to study the effects of BDMC on regulation of epithelial-to-mesenchymal transition (EMT), which is closely linked to tumor cell invasion and metastasis.</p><p><b>METHODS</b>In this study, we first induced transforming growth factor-β1 (TGF-β1) mediated EMT in highly metastatic lung cancer 95D cells. Thereafter, we studied the effects of BDMC on invasion and migration of 95D cells. In addition, EMT markers expressions were also analyzed by western blot and immunofluorescence assays. The contribution of Wnt inhibitory factor-1 (WIF-1) in regulating BDMC effects on TGF-β1 induced EMT were further analyzed by its overexpression and small interfering RNA knockdown studies.</p><p><b>RESULTS</b>It was observed that BDMC inhibited the TGF-β1 induced EMT in 95D cells. Furthermore, it also inhibited the Wnt signaling pathway by upregulating WIF-1 protein expression. In addition, WIF-1 manipulation studies further revealed that WIF-1 is a central molecule mediating BDMC response towards TGF-β1 induced EMT by regulating cell invasion and migration.</p><p><b>CONCLUSIONS</b>Our study concluded that BDMC effects on TGF-β1 induced EMT in NSCLC are mediated through WIF-1 and elucidated a novel mechanism of EMT regulation by BDMC.</p>

Expression and significance of P311 and ITGB4BP in non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to investigate the expression and significance of P311 and ITGB4BP in non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Tissue microarrays were prepared from 80 NSCLC specimens and examined by immunohistochemistry.</p><p><b>RESULTS</b>The positive rates of P311 and ITGB4BP expression were 77.5% (62/80) and 82.5% (66/80), respectively. The double positive expression rate was 73.8% (59/80). The consistency rate was 87.5%, and there was a significant consistency between P311 and ITGB4BP expressions (Kappa = 0.611, P < 0.001).</p><p><b>CONCLUSION</b>There may be a new signaling pathway P311-ITGB4BP in NSCLC, and it may regulate the lung cancer cell migration.</p>

Retrospective analyses of 1 310 cases of lung cancer diagnosed with fibrobronchoscopy / 第三军医大学学报

Objective　To explore the relationship of pathological types of lung cancer with sex, age, site, and clinical diagnosis. Methods　The data of 1 310 patients with lung cancer diagnosed with fibrobronchoscopy, was retrospectively analyzed. Results　①The preliminary clinical diagnosed lung cancers which were comfirmed by fibrobronchoscopic biopsy later were mainly small cell lung cancer. ②The percentage of squamous carcinoma was significantly greater in male (78.0%) than in female (49.7%), but the percentage of adenocarcinoma was significantly higher in female (38.1%) than in male (13.1%)(P<0.0001). ③Among the patients with lung cancer, 53.7% was from 40 to 59 years old and 40.2% over 60. The average age of male patients (56.9 years old) was significantly greater than that of female (51.1 years old) (P<0.0001). ④ The average age of patients with squamous carcinoma and adenocarcinoma was greater in male than in female, but that with small cell carcinoma and squamous carcinoma was greater in female than in male. ⑤The percentage of male with lung cancer in the left lung (37.3%) was greater than that of female (26.0%), but the female had lung cancer in the right lung (59.7%) while male had (49.3%). The left and right upper lobe was more (45.4%) in male, but the right upper and lower lobe was more(43.3%) in female. Conclusion　①The fibrobronchoscopic examination is very important in the diagnosis of lung cancer. ②The pathological types and sites of lung cancer is different in different sex and age, which provide the exact bases for medical and surgical treatment for lung cancer.

Retrospective analyses of 1 310 cases of lung cancer diagnosed with fibrobronchoscopy / 第三军医大学学报

Objective　To explore the relationship of pathological types of lung cancer with sex, age, site, and clinical diagnosis. Methods　The data of 1 310 patients with lung cancer diagnosed with fibrobronchoscopy, was retrospectively analyzed. Results　①The preliminary clinical diagnosed lung cancers which were comfirmed by fibrobronchoscopic biopsy later were mainly small cell lung cancer. ②The percentage of squamous carcinoma was significantly greater in male (78.0%) than in female (49.7%), but the percentage of adenocarcinoma was significantly higher in female (38.1%) than in male (13.1%)(P<0.0001). ③Among the patients with lung cancer, 53.7% was from 40 to 59 years old and 40.2% over 60. The average age of male patients (56.9 years old) was significantly greater than that of female (51.1 years old) (P<0.0001). ④ The average age of patients with squamous carcinoma and adenocarcinoma was greater in male than in female, but that with small cell carcinoma and squamous carcinoma was greater in female than in male. ⑤The percentage of male with lung cancer in the left lung (37.3%) was greater than that of female (26.0%), but the female had lung cancer in the right lung (59.7%) while male had (49.3%). The left and right upper lobe was more (45.4%) in male, but the right upper and lower lobe was more(43.3%) in female. Conclusion　①The fibrobronchoscopic examination is very important in the diagnosis of lung cancer. ②The pathological types and sites of lung cancer is different in different sex and age, which provide the exact bases for medical and surgical treatment for lung cancer.