Dissertation > Excellent graduate degree dissertation topics show

Effects of Bortezomib on the Proliferation、Apoptosis and Adhesive Ability of Lung Adenocarcinoma Cells

Author: TaoHaiYun
Tutor: FanQingXia；LuShiXin
School: Zhengzhou University
Course: Oncology
Keywords: Bortezomib Human Adenocarcinoma Cells Apoptosis NF-κB
CLC: R734.2
Type: Master's thesis
Year: 2009
Downloads: 9
Quote: 0
Read: Download Dissertation

Abstract

Background and ObjectiveLung cancer is a major cause of morbidity and mortality worldwide.And it is also the leading cause of death from cancer.Non-small cell lung cancer（NSCLC） is found in approximately 85%of patients with lung cancer,and the majority of these patients present with unresectable locally advanced or metastatic disease,which are at present incurable.Following the introduction of these new agents and clinical options, great improvements have been achieved,but median survival in advanced NSCLC patients is still poor.Bortezomib is a dipeptidyl boronic acid that functions as a specific and selective reversible inhibitor of the 26S proteasome.Bortezomib has shown its greatest benefit in the treatment of refractory multiple myeloma;it also has been investigated in lung cancer clinical trials,in which it has shown activity as a single agent and in combination regimens,but its mechanism is unclear.MethodsMTT was used to measure the inhibitory effect of bortezomib.Upon exposure of six human lung adenocarcinoma cells（95D、A549、H520、973、H129 and GLC-82） to different concentration（12.5～200nmol/L） of bortezomib for 48 h and 72 h separately,The growth arrest was tested by MTT experiment.At a lower concentration of Bortezomib（25nmol/L） for 48 h,the shape of the cells were observed by inverted microscope;the changes of cell cycle and the apoptosis were assessed by FCM;and the expression of E-cadherin,EGFR,β-catenin and NF-κB level was detected by Western Blot. ResultUpon exposure of six human lung adenocarcinoma cells to different concentration（12.5nmol/L～200nmol/L） of bortezomib for 48 h,IC50 value range from 26～369 nmol/L.While,the 95D cell line is the most sensitive to Bortezomib and the GLC82 cell line is the least one.When extended to 72h,IC50 values of six cell lines are similar and rang from 14 nmol/L to 40 nmol/L.Upon exposure of 6 cell lines to a lower concentration of Bortezomib（25 nmol/L） for 48 h,the morphous change of the cells was observed;and the six cell lines went into G₂/M cell cycle arrest and induced apoptosis.While EGFR and NF-κB expression were downregulated while the protein expression of E-cadherin andβ-catenin were different in different cells.Conclusion1.Bortezomib could inhibit the growth of the six cell lines,with the concentration and time increased,the inhibition reinforced.2.Bortezomib made the six cell lines go into G₂/M cell cycle arrest and induced apoptosis.3.The mechanism may be related to its inhibition on the NF-κB pathway and down regulating the expression of EGFR.4.The protein expression of E-cadherin andβ-catenin were different in different cells, and Bortezomib may be increase the adhesion of the lung cancer cells and reduce distant metastasis.

Effects of Bortezomib on the Proliferation、Apoptosis and Adhesive Ability of Lung Adenocarcinoma Cells

Abstract

Related Dissertations