ABSTRACT
<p><b>BACKGROUND</b>To study the proliferation inhibition and anti-invasion of retinoic acid (RA) and 18β-glycyrrhetinic acid (GA) in highly metastasized lung cancer cell line (PGCL3), and to observe the combined effects of RA and GA.</p><p><b>METHODS</b>The proliferation inhibitive rate, the colony-formation rate in semi-solid agar, the invasive ability to reconstituted basement membrane, the chemotatic migration ability, the laminin adhesion ability, and the activity of cathepsin B (CB) were tested.</p><p><b>RESULTS</b>Treated with RA and GA, the proliferation of PGCL3 cells were inhibited obviously, and the inhibition degree was related to the dosage of the drugs. IC₅₀ of the proliferation inhibition were 12.58 μmol/L and 145.3 μmol/L respectively. Treated with 5.0 μmol/L RA, 25 μmol/L and 50 μmol/L GA, the invasive ability was decreased significantly (P < 0.01 and P < 0.001), and the inhibition was in a dose dependent manner. In combined treatment with 5.0 μmol/L RA and 25 μmol/L GA, the inhibition of invasion was greater than the sum of them used alone. Treated with GA of above concentrations and 10 μmol/L RA, the adhesion and migration ability and the secretion of CB of the PGCL3 cells were decreased significantly (P < 0.001). Treated with GA of above concentation, the colony formation rate in semi-solid agar was decreased significantly (P < 0.001)..</p><p><b>CONCLUSIONS</b>RA and GA can inhibit the proliferation and invasion of the PGCL3 human lung cancer cells and have the anti-invasion synergism. The mechanism of anti-invasion of RA and GA is to inhibit many points of invasive process.</p>
ABSTRACT
<p><b>BACKGROUND</b>To study the anti-invasive effects and its mechanism and apoptosis induction of pentacyclic triterpenoid including glycyrrhizin (GL), 18β-glycyrrhetinic acid (GA), ursolic acid (UA) and oleanolic acid (OA) in highly potentially metastatic lung cancer cell line (PGCL3).</p><p><b>METHODS</b>The invasive ability, the adhesive ability, the migration ability and the activity of cathepsin B (CB) of PGCL3 cells treated with the four drugs were determined by the invasion test of reconstituted basement membrane, the laminin adhesion test, the chemotactic migration test and the enzymological method of CB. The apoptosis of the cells was detected with acridine orange-ethidium bromide fluorescent stain (AO/EB) and TUNEL.</p><p><b>RESULTS</b>The GL,GA, UA and OA could decrease the proliferative ability of PGCL3 cells, and their IC₅₀ values were 1.83 mmol/L, 145.3 μmol/L, 44.73 μmol/L and 40.71 μmol/L respectively. After treatment with 0.5 and 1.0 mmol/L GL, 25 and 50 μmol/L GA, 30 and 40 μmol/L UA, 35 and 45 μmol/L OA for 96 h, the invasive ability of the PGCL3 cells was significantly decreased compared with that of the control groups ( P < 0.01 or P < 0.001). The adhesive and migration ability, the secretion of CB and the colony-formation number in semi solid agar were significantly decreased after PGCL3 cells were treated with the above concentration of the four drugs for 96 h ( P < 0.05, P < 0.01 or P < 0.001), and the inhibition was in a dose-dependent fashion. The percentages of apoptosis of the cells were obviously increased after treatment with the above concentration of the four durgs for 48 h, compared with the control group ( P < 0.05 or P < 0.01).</p><p><b>CONCLUSIONS</b>All of the four drugs can inhibit the proliferative and invasive ability, and induce apoptosis of the PGCL3 human lung cancer cells. The mechanism of anti invasion may be to inhibit the adhesion, migration, and the CB secretion of the cells.</p>