ABSTRACT
Triptolide, a compound extracted from the traditional Chinese medicine preparation of Tripterygium wilfordii Hook F., has been reported to have anti-inflammatory and anti-cancer activities. However, its effect on ovarian cancer invasion is unknown. We observed that MMP7 and MMP19 expression increased in ovarian cancer tissue. Triptolide treatment inhibited the migration and invasion of ovarian cancer cells SKOV3 and A2780 at the concentration of 15 nM. We also observed that triptolide suppressed MMP7 and MMP19 promoter activity in a dose-dependent manner, down-regulating the expressions of these promoters on mRNA and protein level. Moreover, triptolide enhanced E-cadherin expression in ovarian cancer cells. In vivo, triptolide inhibited tumor formation and metastasis in nude mice, and suppressed MMP7 and MMP19 expression; it also enhanced E-cadherin expression in tumor in a dose-dependent manner. Over expression of MMP7 and MMP19, or suppression of E-cadherin expression partially abolished the inhibitory effect of triptolide on invasion of ovarian cancer cells. To summarize, triptolide significantly inhibited the migration and invasion of ovarian cancer cells by suppression of MMP7 and MMP19 and up-regulation of E-cadherin expression. This study shows that triptolide is a good candidate for the treatment of ovarian cancer and reduction of metastasis.
Subject(s)
Animals , Female , Humans , Mice , Antineoplastic Agents, Alkylating/pharmacology , Cadherins/genetics , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Cystadenocarcinoma, Serous/drug therapy , Diterpenes/pharmacology , Epoxy Compounds/pharmacology , Gene Expression Regulation, Enzymologic/drug effects , Matrix Metalloproteinase 7/genetics , Matrix Metalloproteinases, Secreted/genetics , Mice, Inbred BALB C , Mice, Nude , Neoplasm Invasiveness , Ovarian Neoplasms/drug therapy , Paclitaxel/pharmacology , Phenanthrenes/pharmacology , Promoter Regions, Genetic , Up-Regulation/drug effects , Xenograft Model Antitumor AssaysABSTRACT
OBJECTIVE: To compare the hematological effects of carboplatin plus cyclophosphamide, and carboplatin plus paclitaxel chemotherapy for first line treatment of epithelial ovarian cancer (EOC). MATERIAL AND METHOD: A retrospective study was conducted between January 2003 and May 2006 on 29 patients who received 145 cycles of carboplatin, area under the curve (AUC) 6 plus cyclophosphamide 600 mg/mm2 (CC) intravenous and on 11 patients who received 65 cycles of carboplatin AUC 5 plus paclitaxel 175 mg/mm2 (CP) intravenous chemotherapy for the first line treatment of epithelial ovarian cancer. They had no history of hematologic disease and complete blood count (CBC), renal function and liver function tests were normal. RESULTS: Both groups were similar regarding age, body mass index, performance status and stage of cancer. Hematological effects were found in 61 of 145 cycles (42.1%) in CC group and 33 of 65 cycles (50.8%) in CP group (p = 0.05). Twenty patients received all 6 cycles of chemotherapy in the CC group and 10 patients in the CP group. Fifteen of 20 patients (75%) and 8 of 10 patients (80%) had hematologic effect of at least one cycle found in the CC and the CP groups, respectively (p = 0.05). There were no treatment-related deaths in both arms. CONCLUSION: Hematological effects did not differ in carboplatin AUC 6 plus cyclophosphamide 600 mg/mm2 regimen and carboplatin AUC 5 plus paclitaxel 175 mg/mm2 regimen and both regimens were accepted adverse effect in the first line treatment of EOC.
Subject(s)
Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/administration & dosage , Carcinoma, Endometrioid/drug therapy , Cyclophosphamide/administration & dosage , Cystadenocarcinoma, Mucinous/drug therapy , Cystadenocarcinoma, Serous/drug therapy , Female , Hematologic Diseases/chemically induced , Humans , Middle Aged , Ovarian Neoplasms/drug therapy , Paclitaxel/administration & dosage , Retrospective StudiesABSTRACT
Advances in the management of ovarian cancer by use of aggressive surgery and effective platinum-based chemotherapy have prolonged survival; this may have resulted in an alteration of the metastatic pattern of the disease and spread to unusual sites (e.g, CNS) has become more common. Also, with the availability of more sensitive imaging techniques, these tumors are being diagnosed with increasing frequency. Intramedullary spinal cord metastasis is rare. We report one such case treated successfully with chemotherapy and radiotherapy with long-term survival.