Relationship between chemotherapy with paclitaxel, cisplatin, vinorelbine and titanocene dichloride and expression of proliferation markers and tumour suppressor gene p53 in human ovarian cancer xenografts in nude mice.
OBJECTIVE
In this study the relationship between therapy with paclitaxel, cisplatin, vinorelbine and titanocene dichloride and of the expression of proliferation markers (ki67 and S-phase fraction) and tumour suppressor gene p53 was analyzed using a human ovarian cancer xenograft model.


METHODS
Biopsy material from one human ovarian cancer was expanded and transplanted into 102 nude mice. The mice were divided into six groups with different intraperitoneal treatments with paclitaxel, cisplatin, vinorelbine, titanocene dichloride and a control group treated with 0.9% saline solution. After the observation period the tumours were extracted and immunohistochemically stained with monoclonal antibodies against ki67 and p53. The S-phase-fraction was identified by flow cytometry.


RESULTS
There where no statistically significant differences. Regarding the treatment groups, the vinorelbine-group showed the highest percentage (53.3%) and the titanocene dichloride-3x40 mg/kg-group the lowest percentage (7.1%) of ki67-positive specimens, whereas in the control group 35.7% of the specimens were positively stained for ki67. The results for the expression of p53 were similar. The vinorelbine-group had the highest percentage of p53-positive specimens (60%), in both titanocene-groups no specimen showed a positive staining for p53 and in the control group 7.1% of the specimens were positively stained for p53. The mean S-phase-fraction was 14.48% (SD +/- 3.98), no statistically significant relation between S-phase-fraction and expression of p53 (p = 0.883) or of ki67 (p = 0.351) could be shown. The change of tumour volume was independent of the results for ki67, p53 and the S-phase-fraction.


CONCLUSIONS
Although, as previously published, a significant difference of tumour volume change occurred between the treatment groups, in this study we could not find a relation between this change of tumour volume and the expression of p53 or ki67. The absolute number of p53- and ki67-positive staining specimens was too small for statistical analysis, therefore the relevance of the differences between the different treatment groups and the control remains unclear. The results for the S-phase-fraction showed no correlation between the change of tumour volume, different treatment protocols or the expression of p53- and ki67. Our findings contribute to the controversy of the influence of chemotherapy on the expression of proliferation markers and p53.
Kolberg
H C
HC
Department of Gynecology and Obstetrics, University Clinic of Schleswig-Holstein, Campus Lübeck, Germany.
Villena-Heinsen
C
C
Deml
M M
MM
Kraemer
S
S
Diedrich
K
K
Friedrich
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D016158:Genes, p53 / Q000502:physiology; D019394:Ki-67 Antigen / Q000096:biosynthesis; D051379:Mice; D008819:Mice, Nude; D009942:Organometallic Compounds / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D017239:Paclitaxel / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D016196:S Phase / Q000502:physiology; D014183:Transplantation, Heterologous; D014747:Vinblastine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D000077235:Vinorelbine
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D009942:Organometallic Compounds; D014747:Vinblastine; C020528:titanocene dichloride; D017239:Paclitaxel; D002945:Cisplatin; D000077235:Vinorelbine