Highly glycolytic cervical cancers largely resist treatment by cisplatin and co-administered pelvic irradiation as the present standard of care. In this study, we investigated the effects of inhibiting glycolysis and thiol redox metabolism to evaluate them as alternate treatment strategies in these cancers. In a panel of multiple cervical cancer cell lines, we evaluated sensitivity to inhibition of glycolysis (2-DG) with or without simultaneous inhibition of glutathione and thioredoxin metabolism (BSO/AUR). Intracellular levels of total and oxidized glutathione, thioredoxin reductase activity, and indirect measures of intracellular reactive oxygen species (ROS) were compared before and after treatment. Highly radio-resistant cells were the most sensitive to 2-DG, whereas intermediate radio-resistant cells were sensitive to 2-DG plus BSO/AUR. In response to 2-DG/BSO/AUR treatment, we observed increased levels of intracellular oxidized glutatione, redox-sensitive dye oxidation and decreased glucose utilization via multiple metabolic pathways including the TCA cycle. 2-DG/BSO/AUR treatment delayed the growth of tumors composed of intermediate radio-resistant cells and effectively radio-sensitized these tumors at clinically relevant radiation doses both in vitro and in vivo. Overall, our results support inhibition of glycolysis and intracellular redox metabolism as an effective alternative drug strategy for the treatment of highly glycolytic and radio-resistant cervical cancers.
Pharmacology, Toxicology and Pharmaceutical Science
4
5%
Engineering
3
4%
Other
10
13%
Unknown
30
38%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 75. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 February 2018.
All research outputs
#723,447
of 34,350,842 outputs
Outputs from Cancer Research
#376
of 35,807 outputs
Outputs of similar age
#12,829
of 380,777 outputs
Outputs of similar age from Cancer Research
#6
of 194 outputs
Altmetric has tracked 34,350,842 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 97th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 35,807 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.7. This one has done particularly well, scoring higher than 98% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 380,777 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 96% of its contemporaries.
We're also able to compare this research output to 194 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 96% of its contemporaries.
