[Effect of aurora kinase B inhibitor AZD1152 in the treatment of cisplatin-resistant ovarian carcinoma].

OBJECTIVE: To investigate whether AZD1152 (AZD), the selective inhibitor of aurora kinase B, may play a role in the treatment of cisplatin-resistant ovarian carcinoma when administrated alone or in combination with cisplatin. METHODS: Hey (cisplatin-resistant ovarian cancer cell line) cells were analyzed. According to the treatment plan, Hey cells were divided into four groups (AZD group, cisplatin group, AZD + cisplatin group and control group). Methyl thiazolyl tetrazolium (MTT) assay was used to test the cells proliferation, caspase-3/7 activity analysis was used to analyze cells apoptosis, and fluorescence in-situ hybridization (FISH) assay was used to determine the copy the number of chromosome 7 and checked the copy numbers of hTERC gene and C-myc gene. RESULTS: MTT test showed that proliferation of AZD group was lower than that in control group (P < 0.01). The cells proliferation with the treatment with 10 and 20 nmol/L AZD for 24 hours was (81.4 ± 3.6)% and (81.4 ± 3.6)% respectively, and the cells proliferation for 48 hours was (43.1 ± 2.0)% and (38.5 ± 1.6)% respectively, which was significantly lower than control group (100%, P < 0.01); Treated with the same concentration of AZD, inhibition of proliferation was significantly enhanced as the time extended (P < 0.01). Proliferation in group AZD + cisplatin was lower than that in cisplatin group (P < 0.01) which suggest that there were additive effects after combined AZD with cisplatin. Compared with control group, caspase-3/7 activity in AZD group increased significantly (P = 0.000), and the same results was seen between AZD + cisplatin group and cisplatin group or AZD group (all P < 0.01). Compared with cisplatin group or control group, the copy numbers of hTERC, C-myc and the number of chromosome were significantly increased in AZD group and AZD + cisplat group (all P < 0.05). CONCLUSIONS: AZD could inhibit ovarian cancer cells proliferation and induce cells apoptosis significantly. AZD alone or in combination with cisplatin may result in the increased cells polyploidy.

[Study of apoptosis and Fas expression of peritoneal fluid and peripheral blood T lymphocytes in patients with epithelial ovarian cancer and their relationship with CA125].

OBJECTIVE: To investigate the apoptosis and Fas (CD95) expression of T lymphocytes from the peripheral blood and peritoneal fluid of the patients with ovarian cancer and their relationship with CA125. METHODS: Apoptosis and Fas expression of peritoneal fluid and peripheral blood T lymphocytes were assessed by flow cytometry. Peripheral blood samples were obtained from the following objects respectively: patients with stage III - IV ovarian cancer (n = 18) before and after treatment, patients with stage I - II ovarian cancer (n = 15), patients with benign ovarian tumor (n = 18), patients with Krukenberg tumor (n = 6) and normal control (n = 20). Peritoneal fluids were obtained from all the patients with ovarian cancer, Krukenberg tumor and ten patients with benign ovarian tumor. Level of serum CA125 of the patients with ovarian cancer was assessed. RESULTS: In the patients with stage III - IV ovarian cancer, the apoptosis level of the peripheral blood T lymphocytes was 5.55 (3.57 - 9.62)%, significantly higher than those from the patients with stage I - II ovarian cancer, patients with benign ovarian tumor, controls (P < 0.008 in all instances) and the patients with stage III - IV ovarian cancer after treatment (P < 0.05). The intensity of Fas expression of the peripheral blood T lymphocytes from the patients with stage III - IV ovarian cancer was 51 +/- 10, significantly higher than that from controls (P < 0.05). In peritoneal fluid, the apoptosis rates of T lymphocytes, positive rate and intensity of Fas expression on T lymphocytes from patients with stage I - II and stage III - IV ovarian cancer were 17.41 (7.06 - 24.56)%, (57 +/- 16)%, (55 +/- 11)% and 34.06 (17.03 - 44.65)%, (66 +/- 12)%, (70 +/- 24)%, respectively, increased significantly compared with those from patients with benign ovarian tumor, which were 0.78 (0.67 - 1.44)%, (37 +/- 6)%, 43 +/- 6, respectively (P < 0.01 in all instances). The apoptosis level and positive rate of Fas expression on peritoneal fluid T lymphocytes from patients with stage III - IV ovarian cancer were significantly higher than those from patients with Krukenberg tumor (P < 0.01). There was a positive correlation between the serum CA125 level and the apoptosis level of peritoneal fluid T cell in the patients with stage I - II ovarian cancer (r = 0.77, P = 0.009). For ovarian cancer, the apoptosis level of peritoneal fluid T lymphocytes from patients with the serum CA125 > 500 KU/L was higher than that from the patients with the serum CA125 < or = 500 KU/L (P = 0.009). CONCLUSIONS: (1) Extraordinarily increased apoptosis of T cells may play an important role in the development of systemic and celiac immunodeficiency in the patients with ovarian cancer. In contrast with the patients with Krukenberg tumor, the patients with advanced ovarian cancer hare higher percentage of apoptotic peritoneal fluid T lymphocytes, which shows the particularity of local immunity defect. (2) For the patients with ovarian cancer, efficient treatment can decrease the percentage of apoptotic peripheral blood T lymphocytes. (3) The increased positive rate and intensity of Fas expression on peritoneal fluid T lymphocytes stressed the significance of Fas interference in the treatment of ovarian cancer. (4) Level of serum CA125 can reflect the celiac immunity defection in patients with ovarian cancer.