Synergistic effect of indomethacin and NGX6 on proliferation and invasion by human colorectal cancer cells through modulation of the Wnt/beta-catenin signaling pathway.
This study was designed to investigate whether indomethacin and NGX6 synergistically inhibit the growth and invasiveness of human colon cancer cells (HT-29 and SW620) and to elucidate the molecular mechanism of their action. Cell proliferation was assessed by MTT assay. Cell apoptosis was assessed by acridine orange/ethidium bromide staining (AO-EB) and annexin-V-FITC/PI assay. Invasive behaviors of colorectal cancer cells were examined by cell adhesion, migration, and invasion assays. Gap junctional intercellular communication (GJIC) was assessed by the scrape-loading/dye transfer technique. The subcellular localization and expression of beta-catenin protein was examined by immunofluorescence staining and western blot analysis, respectively. Indomethacin and NGX6 had a synergistic effect on inhibiting proliferation and invasiveness of colon cancer HT-29 and SW620 cells, restoring GJIC of HT-29 and SW620, and suppressing translocation of beta-catenin from the nucleus and cytoplasm to the plasma membrane. However, they did not have synergistic effects on enhancing apoptosis and suppressing extracellular matrix adhesion of HT-29 and SW620 cells. Indomethacin and NGX6 inhibit the proliferation and invasiveness of HT-29 and SW620 colon cancer cells by attenuating the WNT/ss-catenin signaling pathway.
Guo
Qin
Q
Department of Digestion Medicine, The Third Affiliated Hospital of Xiang Ya School of Medicine, Central South University, Changsha, 410078, Hunan, People's Republic of China.
Wu
Minghua
M
Lian
Ping
P
Liao
Mantian
M
Xiao
Zhiming
Z
Wang
Xiaoyan
X
Shen
Shourong
S
D000894:Anti-Inflammatory Agents, Non-Steroidal; D017209:Apoptosis / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000473:pathology / Q000628:therapy*; D004357:Drug Synergism; D017629:Gap Junctions / Q000187:drug effects; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D008565:Membrane Proteins / Q000235:genetics / Q000494:pharmacology*; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000494:pharmacology*; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008565:Membrane Proteins; C477325:TMEM8B protein, human; D025521:Tumor Suppressor Proteins; D051153:Wnt Proteins; D051176:beta Catenin; D007213:Indomethacin