Characterization of ovarian cancer cell metabolism and response to chemotherapy by (31)p magnetic resonance spectroscopy.

We aimed to characterize the (31)P magnetic resonance spectra of various ovarian cancer cell lines exhibiting differences in cytotoxic drug resistance. We examined the metabolic profile of three different ovarian cancer cell lines, OC238, A2780, and A2780-cisplatin resistant (A2780cisR), including their response to various cytotoxic drugs (paclitaxel, cisplatin, and carboplatin) by (31)P magnetic resonance spectroscopy (MRS) in vitro. In the OC238 cell line, there were higher levels of phosphorylcholine, phosphodiesters, and uridine diphosphosugar (UDPS) + nicotinamide adenine dinucleotide phosphate (NADP). In A2780 and A2780cisR cell lines, phosphocreatine gave a high signal, which was absent in the OC238 cell line. In the OC238 cell line, a significant decrease in the glycerophosphoethanolamine, glycerophosphocholine, NADP, and UDPS signals was detected following cytotoxic drug treatment, mainly in response to paclitaxel. A significant increase in the glycerophosphocholine signal was detected following exposure to paclitaxel in both A2780 and A2780cisR cell lines. NADP and UDPS signals increased in response to all drugs in the A2780 cell line; however, in the cisplatin-resistant cell line A2780cisR, no significant change in those signals was detected following cisplatin treatment. We conclude that different ovarian cancer cell lines show characteristic (31)P MRS fingerprints and specific metabolic changes in response to cytotoxic drug treatment.

Ex vivo 1H and 31P magnetic resonance spectroscopy as a means for tumor characterization in ovarian cancer patients.

We aimed to determine whether cells obtained from malignant ovarian tumors had different ex vivo 1H- and 31P (phosphorus-31)-magnetic resonance (MR) spectra compared to cells obtained from benign ovarian cysts. In addition, we aimed to assess the metabolic effects of chemotherapy on malignant cells obtained from peritoneal effusions of ovarian cancer patients. We included 20 ovarian cancer patients undergoing explorative laparotomy for tumor resection, 15 patients undergoing oophorectomy for benign ovarian cysts and 8 patients with advanced ovarian cancer with cancerous peritoneal effusion undergoing palliative percutaneous drainage. Ovarian and metastatic tissues were obtained from all patients undergoing laparotomy and analyzed using 1H magnetic resonance spectroscopy (MRS). Cancerous cells from peritoneal effusions were incubated with 3 different anti-mitotic drugs (paclitaxel, cisplatin and carboplatin) at LC50 and the consequent metabolic changes were monitored using 31P-MRS. 1H-MRS revealed significantly higher intracellular lactate levels in cells obtained from ovarian tumors, most prominently in the moderately to poorly differentiated histological types, while total choline (Chol) compounds were higher in the moderately to poorly differentiated subgroup only. Ovarian cancer cells obtained from peritoneal effusions showed a significantly decreased glycerophosphocholine (GPC), glycerophosphoethanolamine (GPE) and uridine diphospho-sugar (UDPS) levels following ex vivo exposure to all 3 anti-mitotic drugs. Ex vivo 1H-MRS identified significant metabolic differences between cells obtained from ovarian tumors compared to those originating in benign ovarian cysts, including increased lactate and total choline compound levels. The 31P-MRS technique allowed characterization and monitoring of metabolic changes occurring in ovarian cancer cells in response to chemotherapy.