Effect of nuclear factor-κB signaling pathway on the expression of hypoxia-inducible factor-1 and vascular endothelial growth factor in nasal polyp cells / 新乡医学院学报

Objective To observe the effect of nuclear factor-κB (NF-κB) signaling pathway on the expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in nasal polyp cells under hypoxic cultivation,and to investigate the relationship between NF-κB signaling pathway and the development of nasal polyp.Methods The nasal polyp and inferior turbinate tissue specimens were collected in the First Affiliated Hospital of Jiamusi University from January 2012 to December 2014.The nasal polyp and inferior turbinate tissues were taken to obtain nasal polyp cells and inferior turbinate cells,then the cells were cultured in primary culture,and the cells were cultured under hypoxia when they grew to 90％.When the cells were cultured in vitro to 90％,the NF-κB inhibitor BAY11-7082 was added (inhibitor intervention group),the other cells without inhibitor were used as controls (no inhibitor group),then the cells in the two groups were cultured under hypoxia.The cells were collected when they were cultured for 0,3,6 and 9 hours,respectively;and the expression of HIF-1α,VEGF and NF-κB p65 protein in the cells were detected by Western blot.Results Compared with 0 hour,the expression of HIF-1α,VEGF and NF-κB p65 protein in nasal polyp cells increased significantly after 3,6 and 9 hours of hypoxic cultivation (P ＜ 0.05);however,the expression of HIF-1α,VEGF and NF-κB p65 protein in inferior turbinate cells was not statistically significant (P ＞ 0.05).The expression of HIF-1α,VEGF and NF-κB p65 protein in nasal polyposis cells after 6 hours of hypoxic cultivation was significantly higher than that after 3 and 9 hours of hypoxic cultivation (P ＜ 0.05);but there was no significant difference in the expression of HIF-1α,VEGF and NF-κB p65 protein in nasal polyp cells between 3 and 9 hours of hypoxic cultivation (P ＞ 0.05).Compared with 0 hour,the expression of HIF-1α and VEGF protein in nasal polyp cells of no inhibitor group increased significantly after 3,6 and 9 hours of hypoxic cultivation (P ＜ 0.05);and the expression of HIF-1α and VEGF protein in nasal polyp cells after 6 hours of hypoxic cultivation was significantly higher than that after 3 and 9 hours of hypoxic cultivation in no inhibitor group (P ＜ 0.05).But there was no significant difference in the expression of HIF-1α and VEGF protein in nasal polyp cells of no inhibitor group between 3 and 9 hours of hypoxic cultivation (P ＞ 0.05).There was no significant difference in the expression of HIF-1 α and VEGF protein in nasal polyp cells of the inhibitor intervention group among 0,3,6 and 9 hours of hypoxic cultivation (P ＞ 0.05).There was no significant difference in the expression of HIF-1α and VEGF protein in nasal polyp cells between no inhibitor group and inhibitor intervention group at 0 hour of hypoxic cultivation (P ＞0.05).The expression of HIF-1α and VEGF protein in nasal polyp cells of inhibitor intervention group was significantly lower than that of no inhibitor group after 3,6 and 9 hours of hypoxic cultivation (P ＜ 0.05).Conclusion The expression of HIF-1α,VEGF and NF-κB p65 protein increased in nasal polyp cells under hypoxia condition.NF-κB signaling pathway may mediate hypoxia-induced HIF-1α and VEGF protein expression,and participate in the occurrence and development of nasal polyp.

Role of long non-coding RNA in drug resistance of tumor / 中国药理学通报

Long non-coding RNA(lncRNA)is a class of RNAs with a number of nucleotides greater than 200,no specific open reading frame and no protein coding. LncRNA could have a sig-nificant influence on the regulation of gene expression during cell growth,and also play a potential role in the development,pro-gression and resistance of tumors. Consequently,it becomes a new tumor research hot spot after miRNA. Many studies have shown that aberrant expression of lncRNA may lead to anti-tumor drug resistance. Furthermore,this resistance is not only derived from individual differences in patients,but also from genetic and epigenetic differences in the tumor. In this paper,we summarize the recent advances in lncRNAs associated with drug resistance that may help overcome drug resistance,so as to improve and develop new therapeutic strategies.

Studies on proliferation and migration effects and mechanisms of M3 mAChR in NSCLC cells / 中国药理学通报

Aim To investigate the effect of M3 mAChR on the proliferation and migration of NSCLC and the molecular mechanisms. Methods CCK-8 as-say,Wound-healing assay and Transwell invasion as-saywere used to determine the cell proliferation,migra-tion and invasion. Calcium imaging was used to identi-fy the M3 mAChR subtype mediating carbachol-in-duced increase in intracellular calcium. Western blot was used to determine the protein level of proliferation, migration and cell cycle related signaling molecules. Results Following the treatment with M3R antagonists 1. 25 ~ 80 μmol · L - 1 for 48 h,the proliferation of NSCLC cells was inhibited,the inhibitory effect:R2-8018 > Darifenacin,H1299 > H460. After the treat-ment with R2-8018,the migration and invasion of H1299 significantly declined. Western blot showed that the protein level of p-Akt,p-GSK3β,cyclinD1 de-clined significantly with the increase of time and that the protein level of p21 increased. Conclusion M3R antagonists induce cell cycle arrest by suppressing the activation of Akt,down-regulating GSK3β and cy-clinD1,and up-regulating p21,then inhibiting the proliferation of NSCLC cells. It also inhibits the inva-sion and migration by down-regulating MMP-2.