Research progress and potential medical applications of anaplastic lymphoma kinase in treatment of non-small cell lung cancer / 中国药理学通报

During the treatment of non-small cell lung cancer ( NSCLC) , many patients have developed drug resistance due to the use of targeted EGFR inhibitors. The main reasons for drug resistance are EGFR site mutations and bypass activation. Activation of ALK pathway is one of the major types of bypass activation. A recent authoritative study indicates that ALK is closely related to immunotherapy. This article reviews the treatment of ALK in tumors from three aspects: the structure and physiological function of ALK, the small molecule inhibitor of ALK, the biological function of ALK and its related treatment methods for NSCLC, and prospects future directions for better application of ALK in the treatment of NSCLC.

Glucose and serum deprivation under hypoxia treatment inducing oxidative stress and apoptosis in rat bone marrow mesenchymal stem cells through inhibition of Nrf2 signaling pathway / 解剖学报

Objective To investigate the effects of glucose and serum deprivation under hypoxia(GSDH)treatment on oxidative stress and apoptosis in rat bone marrow mesenchymal stem cells (BMSCs), so to provide an experimental support for improving the therapeutic efficacy of BMSCs. Methods The cell injury model was established by hypoxia (1% O

Effects of marrow stromal cell-mediated microenvironment on human lung adenocarcinoma A549 cells / 中国病理生理杂志

AIM: To investigate the effects of marrow stromal cell line HS-5 on human lung adenocarcinoma A549 cells in the tumor microenvironment.METHODS:The effects of HS-5 cell-conditioned medium(HS-5-CM)on the viability and migration ability of A549 cells were detected by MTT assay and wound-healing assay.After treatment with HS-5-CM,the expression of CX3C chemokine receptor 1(CX3CR1)at mRNA level in the A549 cells was examined by qPCR. The protein levels of p-ERK and ERK in the A549 cells treated with MAPK/ERK pathway inhibitor U0126 were observed by Western blot,the migration ability of the A549 cells was measured by wound-healing assay,and the protein expression of CX3CR1 was determined by Western blot.RESULTS: HS-5-CM promoted the viability and migration ability of the A549 cells(P<0.01).The expression of CX3CR1 at mRNA level in the A549 cells was increased after treatment with HS-5-CM.MAPK/ERK inhibitor U0126 inhibited the activation of MAPK/ERK signaling pathway(P<0.01), and re-duced the migration ability(P<0.01)and the expression of CX3CR1(P<0.05)in the A549 cells.CONCLUSION:HS-5-CM significantly promotes the A549 cell viability and migration ability.Activation of MAPK/ERK signaling pathway and the expression of CX3CR1 may play a important role in this process.

PGRN gene silencing on proliferation and migration abilities of human non-small-cell lung cancer A549 cells / 中国病理生理杂志

AIM:To investigate the effect of small interfering RNA(siRNA)-mediated progranulin(PGRN) gene silencing on the proliferation and migration abilities of human non-small-cell lung cancer A549 cells and its mecha-nism.METHODS:The mRNA and protein expression levels of PGRN in the A 549 cells and human bronchial epithelial (HBE)cells were detected by qPCR and Western blot.A549 cells were transfected with PGRN-siRNA by liposome meth-od.The expression of PGRN at mRNA and protein levels in the A 549 cells transfected with PGRN-siRNA was detected by qPCR and Western blot, respectively.The cell viability was measured by MTT assay.The cell proliferation ability was measured by living cells counting and crystal violet staining assays.The cell migration ability was measured by wound-heal-ing and Transwell assays.The protein levels of proliferating cell nuclear antigen(PCNA),cyclin D1,Bcl-2 and Bax were determined by Western blot.The protein levels of phosphorylated extracellular signal-regulated kinase 1/2(p-ERK1/2) and phosphorylated protein kinase B(p-Akt)were also determined by Western blot.RESULTS:The expression of PGRN at mRNA and protein levels was higher in the A 549 cells than that in the HBE cells(P<0.05).The expression of PGRN at mRNA and protein levels in the A549 cells transfected with PGRN-siRNA was significantly decreased,and the cell pro-liferation and migration abilities were significantly decreased.The protein expression levels of PCNA,cyclin D1 and Bcl-2 were significantly reduced and the protein expression level of Bax was significantly increased(P<0.05).Meanwhile,the protein levels of p-ERK1/2 and p-Akt were down-regulated(P<0.05).CONCLUSION:PGRN gene silencing obviously inhibits the proliferation and migration abilities of human non-small-cell lung cancer A549 cells.The PI3K/Akt and MAPK/ERK signaling pathways may play an important role in these processes.