| Abstract |
Cholangiocarcinoma (CCA) is a highly aggressive and fatal epithelial cancer that arises
anywhere in the biliary tract. The incidence and mortality rates of CCA are increasing
worldwide and of particular concern in South-east Asia. The majority of CCA patients are
diagnosed at an advanced stage with metastasis and unresectable tumors, where
chemotherapy directed treatment is palliative. Therefore, new therapeutic options are
crucial needed for CCA patients. All-trans-retinoic acid (ATRA), an active metabolite of
vitamin A, is involved in regulation of many necessary biological processes including cell
proliferation, differentiation, and embryonic development. ATRA is an important
differentiation-inducing drug in acute promyelocytic leukemia (APL) treatment. Recently,
ATRA’s anticancer potentials have been shown in several solid cancers such as breast
cancer, prostate cancer, colon cancer, and CCA. However, the anti-metastasis effect of ATRA
in CCA has been largely unknown. The aim of this study was to investigate the effect of
ATRA on cell viability, migration, invasion, adhesion, and the expression of matrix
metalloproteinase 2 (MMP2) gene in KKU-M156 CCA cells.
The result showed that 2.5 µM ATRA treatment decreased cell viability by about
20%, while treatment of the cells with ATRA at 1.25 µM caused no significant toxic effect. At
the dose of 2.5 µM, ATRA treatment for 24h could suppress cell migration with suppression
rate of 61%. Interesting, at the dose of 1.25 µM, ATRA inhibited cell invasion with inhibitory
rate of 43%. Additionally, MMP2 expression was significantly decreased in response to ATRA
treatment (p<0.05). Furthermore, ATRA treatment (1.25-5 µM) decreased the cell adhesive
ability in a concentration-dependent manner (p<0.05).
In summary, ATRA showed anti-metastatic potential in CCA by reducing cell
migrative, invasive and adhesive ability. Additionally, ATRA had an inhibitory effect on MMP2
gene expression. Thus, further research is warranted to investigate the underlying
mechanism for anti-tumor properties of ATRA in CCA. |
Publication
Journal Publication
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