* 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.
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Overview of verb reduce
The verb reduce has 20 senses (first 11 from tagged texts)
1. (102) reduce, cut down, cut back, trim, trim down, trim back, cut, bring down -- (cut down on;
make a reduction in; "reduce your daily fat intake"; "The employer wants to cut back health
benefits")
2. (9) reduce -- (make less complex; "reduce a problem to a single question")
3. (5) reduce -- (bring to humbler or weaker state or condition; "He reduced the population to
slavery")
4. (3) reduce -- (simplify the form of a mathematical equation of expression by substituting one
term for another)
5. (3) reduce -- (lower in grade or rank or force somebody into an undignified situation; "She
reduced her niece to a servant")
6. (3) reduce, come down, boil down -- (be the essential element; "The proposal boils down to a
compromise")
7. (2) shrink, reduce -- (reduce in size; reduce physically; "Hot water will shrink the sweater";
"Can you shrink this image?")
8. (1) reduce -- (lessen and make more modest; "reduce one's standard of living")
9. (1) reduce, scale down -- (make smaller; "reduce an image")
10. (1) deoxidize, deoxidise, reduce -- (to remove oxygen from a compound, or cause to react with
hydrogen or form a hydride, or to undergo an increase in the number of electrons)
11. (1) reduce, tighten -- (narrow or limit; "reduce the influx of foreigners")
12. repress, quash, keep down, subdue, subjugate, reduce -- (put down by force or intimidation; "The
government quashes any attempt of an uprising"; "China keeps down her dissidents very efficiently";
"The rich landowners subjugated the peasants working the land")
13. reduce -- (undergo meiosis; "The cells reduce")
14. reduce -- (reposition (a broken bone after surgery) back to its normal site)
15. reduce -- (destress and thus weaken a sound when pronouncing it)
16. abridge, foreshorten, abbreviate, shorten, cut, contract, reduce -- (reduce in scope while
retaining essential elements; "The manuscript must be shortened")
17. boil down, reduce, decoct, concentrate -- (be cooked until very little liquid is left; "The
sauce should reduce to one cup")
18. reduce, boil down, concentrate -- (cook until very little liquid is left; "The cook reduced the
sauce by boiling it for a long time")
19. dilute, thin, thin out, reduce, cut -- (lessen the strength or flavor of a solution or mixture;
"cut bourbon")
20. reduce, melt off, lose weight, slim, slenderize, thin, slim down -- (take off weight)
Overview of adj reduced
The adj reduced has 2 senses (first 2 from tagged texts)
1. (6) decreased, reduced -- (made less in size or amount or degree)
2. (1) reduced, rock-bottom -- (well below normal (especially in price))
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