ABSTRACT
Targeting kinase inhibitors (TKIs) are effective tools for treating advanced cancer. However, acquired resistance represents a roadblock in the use of TKIs, such as sorafenib, for cancer therapy. Understanding the acquisition of resistance to sorafenib will help doctors to cope with acquired resistance to TKIs in general and to develop personalized medicine strategies for cancer patients. Autophagy is a biological process that occurs in normal organisms. However, it is also a component of multiple disease processes, including cancer development and progression. However, the roles of autophagy in cancer and in response to cancer therapy are controversial. In this review, we summarize the progress in autophagy and sorafenib resistance research, which is representative of acquired resistance to targeted cancer therapy.
Subject(s)
Autophagy/physiology , Lung Neoplasms/drug therapy , Molecular Targeted Therapy/methods , Niacinamide/analogs & derivatives , Phenylurea Compounds/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Animals , Autophagy/drug effects , Autophagy/genetics , Drug Resistance, Neoplasm/genetics , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Niacinamide/therapeutic use , SorafenibABSTRACT
MicroRNAs(miRNA)are a kind of small non -conding RNA,which negative regulate target genes expression at post -transcription level by binding 3'-untraslation region(3'UTR).Dysregulation of miRNA pro-files relate to cancer,immune disorders,cardiovascular disease,neurodegenerative diseases and metabolic diseases. miR -221 /222 are two similary miRNAs,which share the same promoter and have the same seed sequence.miR -221 /222 usually target to same target genes and co -regulate same processes and act as onco -miRNA roles.Howev-er,miR -221 /222 maybe act as suppressor in cancer which maybe dependent particular context.The roles of miR -221 /222 are reviewed in this article,will provide a comprehensive vision for comprehending the biological process of miR -221 /222 in carcinoma.
ABSTRACT
Objective To investigate the expression of DRAM in breast cancer cell line MCF-7 in radiation-induced autophagy. Methods GFP-LC3 transfection method was used to observe autophagy bubble.Real time-PCR was used to detect DRAM and MAPLC3 from transcriptional and translational level,respectively. The silencing vector from gene engineering was introduced by calcium phosphate transfection.Results Compared with the control group,GFP-LC3 increased significantly after 8 Gy irradiation by immunofluorescent assay,and the level of MAP-LC3 expression was higher than control group after 8 Gy irradiation by Western blot ( F =5.38,8.72,10.63,15.23,20.78 and 55.23,P ＜ 0.05 ).DRAM protein expression increased significantly at 2 h in the 8 Gy time-dose study,up to maximum at the 32 h( F =116.34,P ＜ 0.05 ).In DRAM model,the expression of LC3 and DRAM decreased significantly (F =20.36 and 40.35,P ＜ 0.05 ) and DRAM expression increased 8 Gy post-irradiation,but still lower than that in 8 Gy irradiation wild-type group.The LC3 expression also decreasaed 8 Gy post-irradiation(F =50.34,P ＜ 0.05 ).Conclusions DRAM plays an important role in irradiation-induced autophagy in breast cancer cell.DRAM might participate in the process and serve as a theoretical target for clinical treatment of breast cancer.
ABSTRACT
Objective To explore the roles of p53 in ionizing radiation induced MCF-7 cell cycle uncoupling. Methods The p53 knock-down models was established in MCF-7 with retrovirus packaged particles from 293T cells through calcium acid phosphate co-precipitation, then Western blot was used to detect the protein expression. Flow cytometry(FCM) was used to analyze the cell cycle uncoupling and polyploid after irradiation. Results Compared with p53+/+ group, the percentages of G0/G1 cells in p53 -/- group decreased, while those of S and G2+M increased (P < 0.01). In polyploidy analysis 2N cells decreased, whereas both 4N and 8N cells =increased (P<0.01). Compared with sham-irradiation, 4 Gy X-ray led to the decrease of G0/G1, S cells, and the increase of G2+M cells. The increase of 2N cells and decrease of 4N and 8N cells were observed in both p53+/+ and p53-/- cells. Compared with p53+/+ +IR group, the decrease of G0/G1 and S cells and the increase of C2 + M cells were significant (P < 0.01) in p53-/-+ IR groups. 2N cells decreased, 4N cells increased, but no changes in 8 N cells occurred. Conclusion Radiation might induce G2 arrest and cycle uncoupling, p53 plays a role in the regulation of G2 arrest, but no role in cycle uncoupling.
