[The relationship between multi-drug resistance gene expression and drug resistance of ovarian carcinoma].
OBJECTIVE
To study the relationship between multi-drug-resistance (MDR1) gene expression and the drug resistance of ovarian carcinoma and the reversing potency of drug-resistance modifying agent--cyclosporin A (CsA).


METHODS
Tumor-bearing mice of ovarian carcinoma cell (OVCA3) were divided randomly into three groups: control group, adriamycin (ADM) group and ADM +CsA group. The tumor growth rate and the survival rate of mice were investigated and compared among the groups. 32 frozen specimens of ovarian carcinoma tissue from patients were examined for the expression of MDR1 gene by means of RT-PCR.


RESULTS
Ovarian carcinoma cells with positive MDR1 gene expression showed cross drug-resistance to ADM, daunorubicin (DNR), vincristine (VCR) and etoposide (VP-16), the value of inhibiting concentration (IC50) is 4.1-15.5 times of that of the cells with negative MDR1 gene expression. To tumor-bearing mice, there was significant difference in tumor growth rate between mice given combined therapy of CsA + ADM and those given ADM only (P<0.01) Of the 32 frozen specimens of ovarian carcinoma tissue, there was no confirmed relationship between MDR1 gene expression and the pathologic type or differential grade. The possibility of poor prognosis of patients with positive MDR1, gene expression was 16.07 (1.78-144.7) times of that of patients with negative MDR1 gene expression.


CONCLUSIONS
MDR-related drug can induce the overexpression of MDR1 gene and result in the appearance of the multidrug resistance phenomenon. CsA can partially reverse the multidrug resistance of ovarian carcinoma cells both in vitro and in vivo. Detection of MDR1 gene expression in patients of ovarian carcinoma could be used as an index to predict the prognosis of the patients.
Zhu
L
L
Peking Union Hospital, Peking Union Medical College Chinese Academy of Medical Science, Beijing.
Lang
J
J
Shen
K
K
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D003630:Daunorubicin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D019450:Genes, MDR; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D011897:Random Allocation; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014750:Vincristine / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D014750:Vincristine; D004317:Doxorubicin; D016572:Cyclosporine; D003630:Daunorubicin