Alphavbeta 6 integrin inhibits cisplatin-induced apoptosis in ovarian cancer cell lines
Wu, X.-h.; Li, D.-x.; Li, L.; Guo, Y.-h.; Yang, B.; Shan, B.-e.
Zhonghua Fu Chan Ke Za Zhi 39(2): 112-115
2004
ISSN/ISBN: 0529-567X PMID: 15059590 Document Number: 571954
To investigate the effects of alphavbeta6 integrin-mediated cell adhesion on cisplatin (DDP) induced apoptosis in ovarian cancer cell lines. The expression of integrin alphavbeta6 in ovarian cancer cell lines SKOV3, AO, and 3AO was analyzed by flow cytometry, and the apoptosis induced by DDP was measured by enzyme-linked immunosorbent assay (ELISA) method and acridine orange-ethidium bromide (AO-EB) double fluorescent dye staining. Ovarian cancer cell lines SKOV3, AO and 3AO all expressed integrin alphavbeta6. Treated by different concentrations of DDP, SKOV3, AO and 3AO displayed significant apoptosis status compared with the control. However, after cultured in medium containing 10 micro g/ml DDP for 48 hours, SKOV3, AO and 3AO planted on fibronectin (FN)-ligand of alphavbeta6 integrin, had lower enrichment factor (EF), compared with those planted on non-integrin ligand polylisin measured by ELISA method (2.11 +/- 0.04 vs 3.51 +/- 0.03, 2.15 +/- 0.06 vs 3.55 +/- 0.04, 2.11 +/- 0.04 vs 3.66 +/- 0.04, P < 0.01). Similarly, by AO-EB double fluorescent dye staining, lower percentages of apoptosis were found in cells planted on FN (5.0 +/- 0.7)%, (5.0 +/- 0.7)%, (6.0 +/- 0.7)%, than on polylisin (28.0 +/- 0.7)%, (28.0 +/- 0.7)%, (29.0 +/- 0.7)% (P < 0.001). When cells preincubated with integrin alphavbeta6 blocking antibody were planted on FN, the percentages of apoptosis rose again, (15.0 +/- 0.7)%, (16.0 +/- 0.7)%, (15.0 +/- 0.7)% (P < 0.01). The de novo expression of alphavbeta6 integrin occurs in ovarian cancer cell lines SKOV3, AO, and 3AO. alphavbeta6 integrin-mediated cell adhesion to FN can inhibit the effect of cisplatin-induced apoptosis. These results suggest that inhibiting apoptotic cell adhesion may improve drug resistance in ovarian cancer cell lines.