Functional role of the Tau protein in epithelial ovarian cancer cells.

Aim: The microtubule-associated Tau protein is a marker of paclitaxel sensitivity in ovarian cancer. The aim of the present study was to elucidate the function of the Tau protein in epithelial ovarian cancer. Methods: The correlation between Tau protein expression and the response to paclitaxel by using several ovarian cancer cell lines was investigated. Results: A Western blot showed that the expression level of the Tau protein was the highest in the TOV112D cells. A cell-counting kit showed that the proliferation rates were more inhibited in the cells with down-regulated Tau protein than in the control cells, both with and without paclitaxel treatment. The proliferation rates of the control cells and the TOV112D cells also were compared with Tau protein overexpression. The level of cell proliferation was more inhibited in the cells that overexpressed the Tau protein, compared to the control cells, both with and without paclitaxel treatment. It was shown that both the down-regulation and the overexpression of the Tau protein were related to the inhibition of TOV112D cell proliferation. Early and late apoptosis of the TOV112D cells that were transfected with Tau cDNA plasmid construct or Tau small interfering RNA significantly increased. Conclusion: These findings suggest that the molecular targeting of the Tau protein could be a potential treatment for ovarian cancer.

Differences in the sensitivity of ovarian cancer to photodynamic therapy and the mechanisms for those differences.

Protoporphyrin IX (PpIX) levels are crucial to the antitumor action of photodynamic therapy (PDT). In the present study, the underling molecular mechanisms for the variation in PpIX levels in ovarian cancer cells were investigated. Five ovarian cancer cell lines were subcutaneously grafted onto the backs of nude mice. Once tumors had developed, 5-aminolevulinic acid methyl ester hydrochloride (methyl-ALA) was administered intraperitoneally and the tumor was irradiated twice/week. PpIX levels in the tumor were assayed using high-performance liquid chromatography. Enzymes involved in heme synthesis and degradation were screened using a microarray technique. Expression of the glutathione transferase Omega-1 (GSTO1) gene involved in the conversion of PpIX into heme in cells was quantified using the reverse transcription-quantitative polymerase chain reaction. In HTOA, HRA and DISS cells, PDT resulted in significant tumor shrinkage in comparison with the controls. In MCAS and TOV21G cells, no significant alterations in tumor growth were identified compared with the untreated cells. PpIX levels increased significantly in HTOA, DISS and HRA cells compared with in MCAS and TOV21G cells. A comparison of genetic profiles using PDT-sensitive DISS cells and PDT-resistant MCAS cells indicated that MCAS cells exhibited significantly increased levels of δ-aminolevulinate synthase (a rate-limiting enzyme in heme synthesis), heme oxygenase 2 (an enzyme that degrades heme into biliverdin), and biliverdin reductase B (an enzyme that reduces biliverdin into bilirubin) in comparison with DISS cells. The level of GSTO1 expression in HTOA, HRA and DISS cells was ~2.5-fold that in MCAS and TOV21G cells. Sensitivity to PDT is related to PpIX levels in cells. The results of the present study suggested that PpIX tends not to accumulate in PDT-resistant cells despite active heme synthesis and degradation, and that high levels of GSTO1 expression are associated with increased sensitivity to PDT.

A Strategy Using Photodynamic Therapy and Clofibric Acid to Treat Peritoneal Dissemination of Ovarian Cancer.

BACKGROUND: The current study examined the effectiveness of concurrent therapy using photodynamic therapy (PDT) and clofibric acid (CA) to treat peritoneal carcinomatosis resulting from ovarian cancer. MATERIALS AND METHODS: Nude rats were used to create a model of peritoneal carcinomatosis resulting from ovarian cancer and the effectiveness of PDT with 5-aminolevulinic acid methyl ester hydrochloride (methyl-ALA-PDT) was determined. The survival time of rats receiving that therapy was compared to the survival time of a control group. Rats with peritoneal carcinomatosis resulting from ovarian cancer were divided into 3 groups: a group that received debulking surgery (DS) alone, a group that received DS+methyl-ALA-PDT, and a group that received DS+methyl-ALA-PDT+CA. The survival time of the 3 groups was compared. Protoporphyrin, a metabolite of methyl-ALA, produces a photochemical action when activated by light. The level of protoporphyrin (the concentration) that reached organs in the abdomen was measured with HPLC. RESULTS: Rats receiving methyl- ALA-PDT had a significantly longer survival time compared to the controls. Rats with peritoneal carcinomatosis that received DS+methyl-ALA-PDT+CA had a significantly longer survival time compared to the rats that received DS alone. Some of the rats that received concurrent therapy survived for a prolonged period. Protoporphyrin was highly concentrated in peritoneal metastases, but only small amounts reached major organs in the abdomen. PDT was not found to result in necrosis in the intestines. CONCLUSIONS: The results indicated that concurrent therapy consisting of PDT with methyl-ALA and CA is effective at treating peritoneal carcinomatosis resulting from ovarian cancer without damaging organs.