Effect of cis-diammine dichloroplatinum on vascular endothelial growth factor expression in uterine cervical carcinoma.
OBJECTIVE
In this study, we investigated the effects of cis-diammine dichloroplatinum (CDDP) on VEGF mRNA expression and VEGF production in uterine cervical carcinoma tissues obtained from patients with locally advanced disease and in CaSki cells cultured in vitro.


METHODS
VEGF in cultured CaSki cells and in the culture media was measured using a sensitive enzyme-linked immunosorbent assay (ELISA) before and 24 h, 48 h and 72 h after 3 h exposure to CDDP. VEGF mRNA expression in CaSki cells was assessed by the semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) before and 24 h and 48 h after 3 h exposure to CDDP. We also examined the effect of CDDP on microvessel counts in uterine cervical carcinoma tissues obtained before and after high-dose CDDP intraarterial chemotherapy. Immunohistochemical staining using a monoclonal antibody against CD34 was carried out with cervical carcinoma tissue specimens, and microvessel counts were quantified by counting vessels.


RESULTS
CDDP treatment resulted in significant increases in not only VEGF concentrations in cultured CaSki cells and culture media but also in VEGF mRNA expression levels in cultured CaSki cells in a time-dependent and dose-dependent manner compared to untreated controls (p < 0.05, n = 5). On the other hand, VEGF concentrations and microvessel counts in cervical carcinoma tissues were significantly lower in cases with complete response (CR) and partial response (PR), compared to those before treatment (p < 0.05, n = 5 ). By contrast, in cases with no change (NC) to CDDP, both VEGF concentrations and microvessel counts did not decrease and rather showed a somewhat increase compared with levels prior to the treatment.


CONCLUSIONS
These results suggest that CDDP-induced increases in VEGF production by cervical carcinoma cells may stimulate angiogenesis in the tumor lesion after CDDP treatment.
Miyahara
Y
Y
Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Japan.
Yoshida
S
S
Motoyama
S
S
Tateiwa
Y
Y
Hamana
S
S
Maruo
T
T
D018952:Antigens, CD34 / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
D018952:Antigens, CD34; D000970:Antineoplastic Agents; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D002945:Cisplatin