Sirolimus and Metformin Synergistically Inhibits Colon Cancer In Vitro and In Vivo
Journal of Korean Medical Science
;
: 1385-1395, 2017.
Article
in English
| WPRIM
| ID: wpr-200245
ABSTRACT
We estimated the effect of various immunosuppressants (ISs) and metformin (M) to provide theoretical background of optimal therapeutic strategy for de novo colon cancer after liver transplantation (LT). Three colon cancer cell lines (HT29, SW620, and HCT116) were used in in vitro studies. HT29 was also used in BALB/c-nude mice animal models. Following groups were used in both in vitro and in vivo studies sirolimus (S), tacrolimus (T), cyclosporin A (CsA), M, metformin/sirolimus (Met/S), metformin/tacrolimus (Met/T), and metformin/cyclosporin A (Met/CsA). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed and western blot analyses were performed for mTOR pathway proteins, apoptosis proteins, and epithelial-mesenchymal-transition (EMT) proteins. Tumor volume was measured for 4 weeks after inoculation. MTT-assay revealed significant cell viability inhibition in all 3 colon cancer cell lines in groups of S, M, and Met/S. Of note, group Met/S showed synergistic effect compare to M or S group. Western blot analysis showed significant low levels of all investigated proteins in groups of S and Met/S in both in vitro and in vivo experiment. Tumor growth was significantly inhibited only in the Met/S group. Combination of Met and S showed the most potent inhibition in all colon cancer cell lines. This finding might have application for de novo colon cancer.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
In Vitro Techniques
/
Cell Line
/
Cell Survival
/
Blotting, Western
/
Immunosuppression Therapy
/
Liver Transplantation
/
Tacrolimus
/
Cyclosporine
/
Apoptosis
/
Colon
Limits:
Animals
Language:
English
Journal:
Journal of Korean Medical Science
Year:
2017
Type:
Article
Similar
MEDLINE
...
LILACS
LIS