* Lidamycin inhibits tumor initiating cells of hepatocellular carcinoma Huh7 through GSK3β/β-catenin pathway.
- Recently, tumor initiating cells are considered as the central role of tumorigenicity in hepatocellular carcinoma. Enediyne anticancer antibiotic lidamycin with great potential antitumor activity is currently evaluated in Phase II clinical trials. In this study, we evaluated the effect of lidamycin on tumor initiating cells of hepatocellular carcinoma Huh7 and identified the potential mechanism. Flow cytometry analysis and sorting assay, surface marker assay, sphere formation assay, and aldefluor assay were used to evaluate the effect of lidamycin on Huh7 tumor initiating cells in vitro. To investigate the potential mechanism, the activity of GSK3β/β-catenin pathway was detected by Western blot and T cell factors transcriptional activity assay. Subcutaneous tumor model in nude mice was used to observe in vivo effect of lidamycin on Huh7 cells. Lidamycin decreased the proportion of EpCAM+ cells and the expression of EpCAM protein. Lidamycin inhibited sphere formation of sorted EpCAM+ cells in 7 d, and of parental cells in three serial passages. The population of aldehyde dehydrogenase-positive cells was reduced by lidamycin. In addition, lidamycin restrained tumor volume and incidence in vivo. Lidamycin activated GSK3β, and degraded the activity of β-catenin. Consequently, transcriptional activity of β-catenin/T cell factors was decreased. In brief, these results suggest that lidamycin suppressed Huh7 tumor initiating cells via GSK3β/β-catenin pathway. These findings reveal the potential mechanism of lidamycin on tumor initiating cells and the benefit for further clinical evaluation.
=>1.〜に慣れて, 2.用いられた, 中古の
Overview of verb use
The verb use has 6 senses (first 3 from tagged texts)
1. (603) use, utilize, utilise, apply, employ -- (put into service; make work or employ for a
particular purpose or for its inherent or natural purpose; "use your head!"; "we only use Spanish at
home"; "I can't use this tool"; "Apply a magnetic field here"; "This thinking was applied to many
projects"; "How do you utilize this tool?"; "I apply this rule to get good results"; "use the
plastic bags to store the food"; "He doesn't know how to use a computer")
2. (12) use, habituate -- (take or consume (regularly or habitually); "She uses drugs rarely")
3. (8) use, expend -- (use up, consume fully; "The legislature expended its time on school
questions")
4. use -- (seek or achieve an end by using to one's advantage; "She uses her influential friends to
get jobs"; "The president's wife used her good connections")
5. practice, apply, use -- (avail oneself to; "apply a principle"; "practice a religion"; "use care
when going down the stairs"; "use your common sense"; "practice non-violent resistance")
6. use -- (habitually do something (use only in the past tense); "She used to call her mother every
week but now she calls only occasionally"; "I used to get sick when I ate in that dining hall";
"They used to vacation in the Bahamas")
Overview of adj used
The adj used has 3 senses (first 3 from tagged texts)
1. (4) used -- (employed in accomplishing something; "the principle of surprise is the most used and
misused of all the principles of war"- H.H.Arnold & I.C.Eaker)
2. (1) exploited, ill-used, put-upon, used, victimized, victimised -- (of persons; taken advantage
of; "after going out of his way to help his friend get the job he felt not appreciated but used")
3. (1) secondhand, used -- (previously used or owned by another; "bought a secondhand (or used)
car")
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