[Alphavbeta 6 integrin inhibits cisplatin-induced apoptosis in ovarian cancer cell lines].
OBJECTIVE
To investigate the effects of alphavbeta6 integrin-mediated cell adhesion on cisplatin (DDP) induced apoptosis in ovarian cancer cell lines.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Wu
Xiao-hua
XH
Department of Obstetrics and Gynecology, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China.
Li
Dong-xiu
DX
Li
Li
L
Guo
Yan-hong
YH
Yang
Bo
B
Shan
Bao-en
BE
D000951:Antigens, Neoplasm / Q000502:physiology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016023:Integrins / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D016023:Integrins; C073878:integrin alphavbeta6; D002945:Cisplatin