[Experimental study on resistance to cisplatin and taxol in human ovarian cancer SKOV3ip1 multicellular aggregates].
OBJECTIVE
To investigate the chemosensitivity of ovarian cancer SKOV3ip1 multicellular aggregates to cisplatin and taxol and to explore the possible mechanisms accounting for the effect.


METHODS
Liquid overlay system was employed to obtain multicellular aggregates (MCA). We detected the resistance with trypan blue exclusion testing, clonogenic assay, cell cycle profiles and apoptosis with flow cytometry.


RESULTS
MCA cells showed higher cell viability than monolayer cells (P = 0.045 and P = 0.003, respectively). After 40 mumol/L cisplatin exposure for 12 hours, no clone (> or = 50 cells) was formed. After 10 mumol/L taxol exposure for 12 hours, the clone formation showed significant difference in 100-cell group between multicellular aggregates and monolayer cells (P < 0.05). MCA cells in G0 + G1 phase was significantly increased (P = 0.003). After cisplatin exposure, the apoptosis rate of MCA cells were not significantly changed (P = 0.100), and so were cell cycle profiles. Taxol exposure brought about significantly decreased apoptosis rate in MCA cells (P = 0.012). Abrogation of G2 + M arrest was also showed in MCA cells (P = 0.002).


CONCLUSIONS
SKOV3ip1 MCA cells show varying degree but increased resistance to cisplatin and taxol, in particular the latter. Cisplatin has nearly equal cytotoxicity to monolayer and MCA cells. Cell cycle redistribution, abrogation of G2 + M arrest and multicellular-mediated inhibition of apoptosis can partially account for the resistance.
Chen
J
J
Department of Gynecology, Affiliated Hospital of Obstetrics and Gynecology of Fudan University, Shanghai 200011, China.
Feng
Y
Y
Zhou
X
X
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002449:Cell Aggregation; D002453:Cell Cycle / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D017239:Paclitaxel; D002945:Cisplatin