| Research Title |
Inhibition of PI3K/mTOR pathway sensitizes cholangiocarcinoma cells to FGFR inhibitor through cell cycle arrest and apoptotic cell death.
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| Date of Distribution |
22 June 2022 |
| Conference |
| Title of the Conference |
The Science of Successful Ageing: from Physiopharmacological Perspectives and Beyond |
| Organiser |
คณะเภสัชศาสตร์ มหาวิทยาลัยนเรศวร คณะแพทยศาสตร์ จุฬาลงกรณ์มหาวิทยาลัย |
| Conference Place |
Online zoom meeting |
| Province/State |
พิษณุโลก |
| Conference Date |
8 June 2022 |
| To |
10 June 2022 |
| Proceeding Paper |
| Volume |
2022 |
| Issue |
43 |
| Page |
160 |
| Editors/edition/publisher |
|
| Abstract |
An invent Next-generation sequencing has been discovered the fibroblast growth factor receptor (FGFR) alterations as a key driver mutation contributing to cholangiocarcinoma (CCA). Recently, many FGFR inhibitors have been approved to treat metastatic CCA. However, the drug resistance is remained a major obstacle to achieve a better overall survival in CCA patients. This study investigates the concurrent inhibition of FGFR and its main downstream PI3K/mTOR pathway, to suppress the oncogenic phenotypes in CCA model. The CCA cells were treated with a FGFR inhibitor (infigratinib) and a dual PI3K/mTOR inhibitor (PKI-402) for various concentrations and times. The cytotoxicity was determined by SRB assay. Effect of the treatments on antiproliferation, cell death, and cell cycle arrest were determined using AO/EB staining and flow cytometry. The results of antiproliferative assay showed combination treatment of infigratinib and PKI-402 exerted more cytotoxicity on CCA cells than either single agent treatment. In addition, PKI-402 significantly enhanced antiproliferative effect of infigratinib through G2/M cell cycle arrest in KKU-M213A cells. More importantly, a combined treatment showed more potent to promote apoptotic inducing effect in CCA cells while the single agent caused less effect on apoptosis (less than 3%). Our study revealed that combined inhibition of FGFR and PI3K/mTOR pathways could be a promising therapeutic strategy to improve the treatment outcomes especially for FGFR inhibitors. |
| Author |
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| Peer Review Status |
มีผู้ประเมินอิสระ |
| Level of Conference |
ชาติ |
| Type of Proceeding |
Abstract |
| Type of Presentation |
Poster |
| Part of thesis |
true |
| Presentation awarding |
false |
| Attach file |
|
| Citation |
0
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Publication
Journal Publication
ไทย