Autophagy Regulated by Gain of Function Mutant p53 Enhances Proteasomal Inhibitor-Mediated Cell Death through Induction of ROS and ERK in Lung Cancer Cells

Figure 1

GOF-R273H-p53 mutation imparts drug resistance. (a) Cell lines with varied p53 status were exposed to different doses of cisplatin. Cell viability was analyzed after 48 h of treatment through MTT assay. Untreated samples were taken as control. and # indicate significant difference compared to untreated cells and R273H-P53 cells, respectively. (b) Fold change in caspase-3 enzyme activity was measured following CDDP treatment at IC-50 dose for 48 h in H1299 (null-P53) and H1299-R273H-P53 stable transfected cells. Level of caspase-3 activity in untreated control was taken as arbitrary unit “1.” (c) DNA fragmentation was measured on agarose gel. Null-P53 and R273H-P53 cells were treated with CDDP at low dose (LD) and IC-50 dose for 48 h; DNA was extracted and run on an agarose gel. A DNA marker was run alongside the samples. (d) Real-time PCR showing expression of ABCB1 mRNA levels upon exposure of null-P53 and R273H-P53 cells to CDDP (IC-50) for 48 h. (e) Null-P53 and R273H-P53 cells were given different doses of 5-FU and cross resistance was analyzed through MTT assay. indicates significant difference compared to untreated cells.

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