249P - Galectin-3 promotes cell proliferation and attenuates cytotoxic effect of paclitaxel via ERK signaling pathway in gastric cancer cells

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Cytotoxic agents
Cancer biology
Gastric Cancer
Presenter Nobuko Serizawa
Citation Annals of Oncology (2016) 27 (suppl_9): ix68-ix85. 10.1093/annonc/mdw582
Authors N. Serizawa1, A. Nagahara2, S. Yamashina3, Y. Inami1, S. Watanabe1
  • 1Gastroenterology, Juntendo University Hospital, 1130022 - Tokyo/JP
  • 2Gastroenterology, Juntendo University Shizuoka Hospital, Shizuoka/JP
  • 3Gastroenterology, Juntendo University Hospital, Tokyo/JP

Abstract

Background

Galectin-3 (gal-3), which is a β-galactosidase binding lectin, is highly expressed in gastric cancer cells and modulates cell proliferation. Paclitaxel, which stabilizes the microtubule, has much broader activity such as modulation of mitogen-activated protein kinase (MAPK) signaling pathway. Our aim in this study is to elucidate the mechanism by which gal-3 may contribute to cell proliferation and to assess whether silencing of gal-3 enhances the cytotoxic effect of paclitaxel on gastric cancer cell proliferation via MAPK pathway.

Methods

MKN-45 (Human gastric cancer cell) was transfected with gal-3 or scrambled (scr) siRNA, and 48 hours later the following experiments were performed in each condition. Gal-3 expression was by western blotting. After 10 minutes of exposure to Epidermal Growth Factor (EGF), cell proliferation was assessed by CCK-8. Extracellular Signal-regulated Kinase (ERK) phosphorylation was tested as a downstream target by western blotting. Cell proliferation was tested by CCK-8 and ERK phosphorylation was tested by western blotting in the presence or absence of paclitaxel in each condition in order to assess downstream signaling pathway.

Results

The number of proliferating cells was significantly lower in gal-3 siRNA transfected cells than those transfected with scr siRNA, suggesting that gal-3 plays a role in gastric cancer cell proliferation. After EGF exposure, phosphorylation of ERK was reduced in gal-3 siRNA transfected cells, indicating that gal-3 is inducing ERK mediated signaling pathway. When paclitaxel was used in combination with gal-3 or scr siRNA transfected cells, proliferating cells were significantly decreased in gal-3 siRNA/paclitaxel combination compared to scr siRNA/paclitaxel combination, suggesting that silencing gal-3 enhances the paclitaxel effect on gastric cancer cell proliferation. ERK phosphorylation was reduced in gal-3 siRNA/paclitaxel combination compared to scr siRNA/paclitaxel combination, indicating that gal-3 attenuates cytotoxic effect of paclitaxel via ERK signaling pathway in gastric cancer cells.

Conclusions

Gal-3 promotes cell proliferation and attenuates cytotoxic effect of paclitaxel via ERK signaling pathway.

Clinical trial indentification

Legal entity responsible for the study

N/A

Funding

N/A

Disclosure

All authors have declared no conflicts of interest.