Page 93 - D. Cancer biology

Cancer stem cells targeted therapy through inhibition of LPA pathway
in ovarian cancer stem cells

MinJoo Shin, DaeKyoung Kim, SeoYul Lee, YeEun Kim, and JaeHo Kim
Department of Physiology, School of Medicine, Pusan National University, Yangsan- si,50612
BACKGROUND

Ovarian cancer shows high mortality due to development of resistance to chemotherapy and relapse. Cancer stem
cells are a subpopulation of cancer cells characterized by self-renewal ability, tumorigenesis and drug resistance. In
previous studies, we have shown that autotaxin and lysophosphatidic acid (LPA) play an important role in cancer
stem cell characterization such as migration, sphere forming ability and drug resistance in ovarian cancer. So in this
study, we found a drug that could target cancer stem cells by inhibiting the LPA pathway. When the LPA inhibitor
was treated with A2780-SP, sphere-forming ability was significantly reduced compared to the treatment with
KI16425 and Paclitaxel. When ovarian cancer stem cells and paclitaxel were treated with ovarian cancer cells,
cancer cells showed low survival rate even at low concentration and cancer stem cells showed high survival rate
even at high concentration. However, when LPA inhibitor was treated with ovarian cancer stem cells and ovarian
cancer cells, survival rate was much lower in cancer stem cells than in cancer cells. It was confirmed that ovarian
cancer stem cells isolated from ovarian cancer patients had the same results as cell lines. In addition, after
processing LPA inhibitor at different concentrations was confirmed that a concentration-dependent manner the
expression is reduced when the check ABC transporter such as ABCB1 and ABCG2 by western blot. When the cell
death was confirmed by FACS analysis, it was confirmed that the cells were killed more by the lpa inhibitor
treatment as in the previous results. These results suggest that the LPA inhibitor may be an effective drug for the
treatment of ovarian cancer stem cells.
RESULTS

FIGURE 3. The effect of new LPA FIGURE 5. The analysis of FIGURE 6. FIGURE 5. The
receptor inhibitors on the cell death of cell apoptosis by LPA analysis of cell apoptosis
ovarian cancer stem cells. receptor BECK35 inhibitor by LPA receptor BECK35
in ovarian cancer cells by inhibitor in ovarian cancer
FACS. stem cells by FACS.

FIGURE 1. The role of ATX-LPA-Akt1
signaling in proliferation, migration,
and anticancer drug resistance of FIGURE 7. Isolation of patient-derived ovarian cancer
ovarian cancer stem cell. stem cell.

FIGURE 4. The influence of LPA receptor
FIGURE 2. The effect of Ki16425 (LPA BECK inhibitors on ovarian cancer and
Receptor Inhibitors) on the cell ovarian cancer stem cells.
apoptosis of ovarian cancer stem FIGURE 8. The influence of LPA receptor BECK
cells. inhibitors on patient-derived ovarian cancer stem
cell.
CONCLUSION Contact information

LPA pathway has a great effect on the characteristics of ovarian cancer stem cells. Department of Physiology, School of
We have found that the LPA receptor inhibitor is more effective in reducing Medicine, Pusan National University,
ovarian cancer stem cell characteristics than ovarian cancer cells. The LPA inhibitor Yangsan- si,50612
reduced cell viability, regulated the expression of the ABC transporter, and
reduced the size of the sphere in ovarian cancer stem cells. We cultured ovarian shinmj90@gmail.com
cancer stem cells using cancer cells isolated from ovarian cancer patients. Similar +82-051-510-8070
results were obtained with ovarian cancer stem cell experiments in ovarian cancer
patients.
lpa inhibitor is more effective for ovarian cancer stem cells than for ovarian cancer
cells, suggesting that it may be a more effective and new treatment for ovarian
cancer stem cell therapy.