Targeting Medium-Chain Acyl-CoA Dehydrogenase (MCAD) for Glioblastoma (GBM) Downregulation of MCAD resulted in severe mitochondrial failure in GBM and longer animal survival
MCAD-knockdown dramatically attenuated tumor growth using GSC8.11 and GSC6.27.
Downregulation of MCAD impaired mitochondrial function
Lipid accumulation and reactive oxygen species (ROS)-related damage in MCAD-knockdown GSCs
GSC 6.27
GSC 8.11
oxygen consumption rate significantly decreased in basal respiration and reserve respiratory capacity in ACADM -deleted GSCs
GSC 8.11 xenograft tumor tissues showed lipid accumulation upon ACADM silencing
12 weeks
4 weeks
4 weeks
8 weeks
- DOX
+ DOX
MCAD-knockdown significantly extended survival time.
MCAD-knockdown GSC 8.11 partially rescued in fatty acid free medium (left) and by GSH (right)
decrease in ATP content in MCAD-depleted GSCs
GSC 8.11
P= *0.0321 *0.0164
sh-ctrl
ATP
100
1.5
GSC 8.11
sh-ACADM1
sh-ctrl sh-ctrl + GSH sh-ACADM1 sh-ACADM1 + GSH
150000
**
**
sh-ACADM2
100000
1.0
50
50000
0.5
*
*
P< 0.0001
0
0
2
4
6
7
0
Time (Days)
0.0
Time (weeks) 4 6 8 10 12 14
sh-ctrl
sh-ACADM1 sh-ACADM2
Nov. 17-18, 2022
2
MD Anderson Cancer Center
Made with FlippingBook - Online magazine maker