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Chinese materia medica can inhibit the proliferation, invasion, migration and expression of drug-resistant proteins of lung cancer stem cells (LCSCs), and induce apoptosis and delay self-renewal, as well as exert anti-tumor effects by interfering with their ecological niche, immune microenvironment and aerobic glycolysis, etc. The biomarkers involved mainly include CD133, CD44, ALDH and ABCG2, while the related signaling pathways are Wnt/β-catenin, Hedgehog, and Notch. The research on the intervention of LCSCs by Traditional Chinese Medicine (TCM) is generally few, mostly concentrated in basic research, and the selected experimental indicators have a high repetition rate, involving fewer cell types and signaling pathways; there is a relative lack of clinical trials, which lack an organic connection with basic experiments. In the future, the quality of research is expected to be improved, and in-depth study of TCM with anti-lung cancer stem cell effect should be carried out, with the purpose to promote the precise treatment of lung cancer.
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ObjectiveTo investigate effect of lyophilized powder of modified Huangqi Gancaotang on proliferation， apoptosis， invasion， migration， and epithelial-mesenchymal transition of human non-small cell lung cancer cells （A549， PC9） and possible mechanism. MethodEffect of 1.0， 2.0， 4.0， 8.0， 12.0 g·L-1 modified Huangqi Gancaotang on the proliferation of non-small cell lung cancer cells was detected by cell counting kit-8 （CCK-8） assay. A549 and PC9 cells were classified into the blank group and the low-， medium-， and high-dose Huangqi Gancaotang groups （2.0， 4.0， 8.0 g·L-1）. Plate cloning assay was used to examine the effect of modified Huangqi Gancaotang on cell cloning ability. Hoechst 33342 staining and flow cytometry were employed to detect the apoptosis， and scratch assay and Transwell migration assay were applied to examine cell migration and invasion abilities， respectively. Mammosphere assay was used to examine the sphere-forming ability of tumor cells， and real-time polymerase chain reaction （Real-time PCR） to detect the mRNA expression of stemness-related molecules octamer-binding transcription factor 4 （Oct-4）， human sex-determining region Y-box 2 （Sox2）， and homeobox transcription factor （Nanog） to assess cancer stem cell activity. The protein expression of B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated death promoter （Bad）， Bcl-2-associated X protein （Bax）， cleaved Caspase-3， Caspase-3， E-cadherin， N-cadherin， vimentin， matrix metalloproteinase-2 （MMP-2）， β-catenin， c-Myc， Cyclin D1， and zinc-finger transcription factor （Slug） was determined by Western blot. ResultThe proliferation ability of A549 and PC9 cells was significantly inhibited after 24 h and 48 h treatment with 1.0， 2.0， 4.0， 8.0， and 12.0 g·L-1 lyophilized powder of modified Huangqi Gancaotang compared with that in the blank group and the inhibition was dose- and time-dependent （P<0.05， P<0.01）. Compared with the blank group， the low-， medium-， and high-dose modified Huangqi Gancaotang suppressed the cloning ability of A549 and PC9 cells （P< 0.05， P<0.01）， and high-dose modified Huangqi Gancaotang induced apoptosis of A549 and PC9 cells （P<0.01）. In comparison with the blank group， the low-， medium-， and high-dose modified Huangqi Gancaotang inhibited the invasion and migration of A549 and PC9 cells （P<0.05， P<0.01）. Compared with the blank group， the low-， medium-， and high-dose modified Huangqi Gancaotang significantly decreased volume of the microspheres of A549 cells and the mRNA expression of Oct-4， Sox2， and Nanog in A549 and PC9 cells （P<0.05， P<0.01）. Compared with the blank group， the medium- and high-dose modified Huangqi Gancaotang down-regulated the expression of the anti-apoptotic protein Bcl-2 （P<0.05， P<0.01）， up-regulated the expression of pro-apoptotic proteins Bad， Bax， and cleaved Caspase-3/Caspase-3 （P<0.05， P<0.01） in A549 and PC9 cells， decreased the expression of MMP-2， N-cadherin， and vimentin （P<0.05， P< 0.01）， and raised the E-cadherin expression （P<0.05， P<0.01）. Moreover， the medium-dose and high-dose modified Huangqi Gancaotang all reduced the expression of β-catenin， c-Myc， Cyclin D1， and Slug in A549 and PC9 cells （P<0.01）. ConclusionModified Huangqi Gancaotang can inhibit the proliferation， invasion， migration， activity of cancer stem cells， and epithelial-mesenchymal transition of human non-small cell lung cancer （A549， PC9） cells and induce apoptosis， and the mechanism is the likelihood that it regulates Wnt/β-catenin signaling pathway.
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Mesoporous silica nanoparticles as drug carrier have become the new hot point in the field of biomedical application in recent years. This review focuses on the more recent developments and achievements on experimental design aspect of mesoporous silica nanoparticles with cancer diagnosis and therapy. The key advances of functionalization strategies of mesoporous silica nanoparticles with controlled release, tumor targeting and overcoming multidrug resistance are discussed in particular. Mesoporous silica nanoparticles as unique delivery systems have the potential to provide significantly a sound platform for cancer theranostic application.
Subject(s)
Animals , Humans , Antineoplastic Agents , Therapeutic Uses , Delayed-Action Preparations , Drug Carriers , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Nanoparticles , Neoplasms , Diagnosis , Therapeutics , Porosity , Silicon DioxideABSTRACT
<p><b>OBJECTIVE</b>To investigate the correlation between expression of A-kinase anchoring protein 95 (AKAP95) and protein expression of cyclin E1 and cyclin D1 in lung cancer tissue.</p><p><b>METHODS</b>Fifty-one cases of lung cancer were included in the study. The protein expression of AKAP95, cyclin E1, and cyclin D1 were measured by immunohistochemistry.</p><p><b>RESULTS</b>The protein expression of cyclin E1 in lung cancer tissues was significantly higher than that in para-cancerous tissues (positive rate: 75.56%vs 20%, P < 0.01); its expression showed no relationship with histopathological type, lymph node metastasis, and cellular differentiation (P > 0.05). The protein expression of cyclin D1 in lung cancer tissues was higher than that in para-cancerous tissues (positive rate: 69.39% vs 14.29%); its expression showed a significant relationship with histopathological type (P < 0.05). The expression of AKAP95 was correlated with the protein expression of cyclin E1 and cyclin D1 in lung cancer tissues (P < 0.01).</p><p><b>CONCLUSION</b>Cyclin E1 and cyclin D1 are highly expressed in lung cancer tissue, suggesting that they play an important role in the development and progression of lung cancer. The protein expression of cyclin E1 has no relationship with cellular differentiation, lymph node metastasis, and histopathological type of lung cancer, and the protein expression of cyclin D1 has a significant relationship with histopathological type. The expression of AKAP95 is correlated with the protein expression of cyclin E1 and cyclin D1 in lung cancer tissue.</p>
Subject(s)
Adult , Aged , Humans , Middle Aged , A Kinase Anchor Proteins , Metabolism , Cyclin D1 , Metabolism , Cyclin E , Metabolism , Lung , Metabolism , Pathology , Lung Neoplasms , Metabolism , Pathology , Oncogene Proteins , MetabolismABSTRACT
Objective To explore the possibility of finding pulmonary embolish by CT scan. Methods 20 cases of patients with pulmonary embolism comfirmed by CTA were selected. The CT scan was compared with the enhance film in the same level of contrast observation site. Results 12 cases found in plain site with the CTA form show abnormal density within the same lumen shadow. Indirect signs of bronchial artery dilatation except plain and outside the CTA showed no difference. Conclusion Pulmonary embolism in the carefully observed before enhanced large artery can be found within the thrombus.