| Abstract |
Objective: To investigate the mechanism of resistance and reversal effect
of ligustrazine and cyclosporin A in cisplatin-induced multidrug
resistance ovarian cancer cell line 3Ao/cDDP.
Methods: Using the corresponding dose calculated from clinical
chemotherapy at 30 mg cisplatin per cycle, we established 3Ao/cDDP with
3Ao exposed at regular intervals and repeatedly to high-level
concentration of cisplatin at 10 mug/ml for 24 hours each time.
Expressions of LRP, MRP, P-gp, GSTp and TopoII were quantitatively
detected with FCM. For drug resistance reversal, cyclosporin A and
ligustrazine were administered singly or in combination at the maximal
dose without cytotoxicity. Inhibition rates were determined by MTT assay.
Results: 3Ao/cDDP was established after 4.5 months, with resistance factor
1.6 which was similar to clinical resistance degree. Low expression levels
of MRP and P-gp were found in both 3Ao and 3Ao/cDDP (P>0.05), and LRP and
GSTx expression levels in 3Ao/cDDP were significantly higher than those in
3Ao (P<0.005 and P<0.05, respectively), and TopoII in 3Ao/cDDP was
significantly lower vs 3Ao (P<0.05). The inhibition rate of cDDP was 20.
807 +- 0.015%, cDDP plus iigustrazine 27.421 +- 0.07% (P>0.05 vs cDDP), cDDP
plus cyclosporin A 49.635 +- 0.021% (P<0.01 vs cDDP), and cDDP plus
ligustrazine and cyclosporin A 58.861 +- 0.014% (P<0.01 vs cDDP).
Conclusions: 3Ao/cDDP, induced by cisplatin and established by imitating
the characteristics of clinical chemotherapy for epithelial ovarian
cancer, was an ideal model for investigation of cisplatin resistance in
vitro. Cisplatin resistance in 3Ao/cDDP could be accounted for by higher
LRP, GSTp and lower TopolI expression and was not associated with MRP or
P-gp. Ligustrazine had no significant reversal effect on cisplatin
resistance, but cyclosporin A could reverse the resistance effectively.
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