Effects of simvastatin in combination with anticancer drugs on proliferation and migration in cholangiocarcinoma cells
By: Buranrat, Benjaporn
.
Contributor(s): Senggunprai, Laddawan.
Publisher: Mumbai Indian Journal of Pharmaceutical Science 2022Edition: Vol.84(1), Jan-Feb.Description: 72-79p.Subject(s): PHARMACEUTICSOnline resources: Click here
In:
Indian journal of pharmaceutical sciencesSummary: Developing new treatment options for cholangiocarcinoma is necessary because of the adverse drug reactions
and drug resistance problems associated with current chemotherapeutics. Therefore, this study examined
cytotoxic, apoptotic and antimigratory effects of simvastatin used in combination with anticancer drugs
(5-fluorouracil and cisplatin) against human cholangiocarcinoma cells and investigated the underlying
molecular mechanism (s) of action. Proliferation, apoptosis and migration of cholangiocarcinoma cells were
determined by sulforhodamine B, flow cytometry, colony formation, reactive oxygen species formation,
caspase 3 activity, wound healing and western blotting. We observed that the two test statins, simvastatin
and atorvastatin, enhanced 5-fluorouracil and cisplatin cytotoxicity against cholangiocarcinoma cells,
simvastatin showed the higher effects than atorvastatin. Further, simvastatin plus 5-fluorouracil and
cisplatin decreased colony formation and in combination induced p21 and reduced cyclin D1 protein.
Furthermore, combination treatment augmented the apoptosis of cholangiocarcinoma cell through
stimulating reactive oxygen species generation and caspase 3 activity as well as upregulating caspase
3 levels. Simvastatin also potentiated antimigratory effect of anticancer drugs via reduction in matrix
metalloproteinase 9 levels. Accordingly, the combination of simvastatin with anticancer drugs could be
considered a novel strategy to expand treatment options for cholangiocarcinoma.
| Item type | Current location | Call number | Status | Date due | Barcode | Item holds |
|---|---|---|---|---|---|---|
Articles Abstract Database
|
School of Pharmacy Archieval Section | Not for loan | 2022-2221 |
Developing new treatment options for cholangiocarcinoma is necessary because of the adverse drug reactions
and drug resistance problems associated with current chemotherapeutics. Therefore, this study examined
cytotoxic, apoptotic and antimigratory effects of simvastatin used in combination with anticancer drugs
(5-fluorouracil and cisplatin) against human cholangiocarcinoma cells and investigated the underlying
molecular mechanism (s) of action. Proliferation, apoptosis and migration of cholangiocarcinoma cells were
determined by sulforhodamine B, flow cytometry, colony formation, reactive oxygen species formation,
caspase 3 activity, wound healing and western blotting. We observed that the two test statins, simvastatin
and atorvastatin, enhanced 5-fluorouracil and cisplatin cytotoxicity against cholangiocarcinoma cells,
simvastatin showed the higher effects than atorvastatin. Further, simvastatin plus 5-fluorouracil and
cisplatin decreased colony formation and in combination induced p21 and reduced cyclin D1 protein.
Furthermore, combination treatment augmented the apoptosis of cholangiocarcinoma cell through
stimulating reactive oxygen species generation and caspase 3 activity as well as upregulating caspase
3 levels. Simvastatin also potentiated antimigratory effect of anticancer drugs via reduction in matrix
metalloproteinase 9 levels. Accordingly, the combination of simvastatin with anticancer drugs could be
considered a novel strategy to expand treatment options for cholangiocarcinoma.
Click on an image to view it in the image viewer
There are no comments for this item.