Inhibitory Effect Of Aspirin On Ovarian Carcinoma SKOV3 In Vivo

Objective:Ovarian carcinoma seriously threatens female health and the mortality caused by it is mostly in all kinds of woman malignant tumors. Presently the treatment, including of surgery and chemotherapy, can't reach the expectant goal of prolonging patient'life farthest because the early diagnoses is difficult, the curative effect isn't good in an advanced stage, and ovarian carcinoma may be recrudesce after operation. Therefore it is imperative under this situation to establish a new measure of prevention and cure.Aspirin, as a kind of non-steroidal anti-inflammatory drug (NSAID), can restrain the effect of cyclooxygenases(COXs) and play down synthesization of prostaglandians(PGs). Recently the domestic and overseas researches demonstrate that aspirin can be viewed as a chemoprophylaxis drug of anticancer .But most researches are concentrated in the effect of aspirin on multiplication and apoptosis of cellular system in vitro. Few reports about inhibitory effect of aspirin on ovarian carcinoma can be found.In this research, SKOV3 cells (Human ovarian carcinoma cell lines) were cultured in vitro and established the model of human ovarian carcinoma transplanted subcutaneously in nude mice. The purpose of this research was to investigate the inhibitory effect of aspirin on cellular apoptosis, to observe the expression of cyclooxygenase-2(COX-2), vascular endothelial growth factor(VEGF) and microvassel density(MVD) of the transplanted tumor, to detect the relationship between inhibitory effect of aspirin on COX-2 and vascular interrelated growth factor, to investigate the mechanism of aspirin on prevention and cure of ovarian carcinoma.Methods:SKOV3 cells(Human ovarian carcinoma cell lines) were cultured in vitro, to establish the model of human ovarian carcinoma SKOV3 transplanted subcutaneously in nude mice. Divided 25 nude mice into 5 groups random: control group, aspirin 15mg/kg group, aspirin 25mg/kg group, aspirin 25mg/kg plus CTX 100mg/kg group, CTX 100mg/kg group. The tumor volumes are measured every 3 days and draw the tumor growth curve by the ending of the experiment on the 21st day. The formation rate, tumor weight and inhibitory rate of each group were observed. Apoptosis rate and cell cycle of the SKOV3 transplanted tumor were assessed in each group by FCM. Histopathological examination was also conducted by microscope. Immunohistochemsitry was used to investigate the influence aspirin on the expression of COX-2,VEGF and MVD in tumor tissue.Result:1 The growth curve of human ovarian carcinoma SKOV3 transplanted subcutaneously in nude mice: Compared to control group, others therapy groups all showed suppressive effect on tumor growth and the most obviously is aspirin plus CTX group.2 Comparison of the tumor volume in different groups: Tumor volumes in each therapy group were smaller than those in control group(P<0.01). It was no significantly for the therapy group to compare with each other random(P>0.05).3 Tumor weight and inhibitory percent:Tumor weights in control group were bigger than those in each therapy group(P<0.01). Tumor weights in aspirin 25mg/kg group were bigger than those in aspirin 25mg/kg group(P<0.05).Tumor weights in aspirin plus CTX group were bigger than those in CTX group(P<0.05).It was the inhibitory percent of therapy groups that showed in aspirin 15mg/kg group was 48.82%, in aspirin 25mg/kg group was 56.17%, in aspirin plus CTX group was 81.63%, in CTX group was 73.23%.4 Assessed the apoptosis percent of the transplanted tumor in each group by FCM: It was the apoptosis percent of each group that showed in control group was 7.95±1.45%, in aspirin 15mg/kg group was 9.73±1.38%, in aspirin 25mg/kg group was 13.61±0.41%, in aspirin plus CTX group was 25.86±2.19%, in CTX group was 24.03±0.43%. Compared to control group, it was significantly for each therapy group(P<0.01). The apoptosis percent in aspirin 25mg/kg group was higher than that in aspirin 15mg/kg group(P<0.05). The apoptosis percent in aspirin plus CTX group was higher than that in CTX group(P<0.05). 5 Histopathological examination was also conducted by microscope: It could be found in control group such as the denseness of ovarian carcinoma cells, cellular variation, obvious nucleolus, much karyostenosis and angiogenesis. In therapy groups, contractible karyons and a mass of cellular death were able to be observed. In all groups, necrotic proportion which reached 40%~50% was the highest in aspirin plus CTX group.6 The expression of COX-2 in transplanted tumor tissue: In treated groups including of control group, aspirin 15mg/kg group, aspirin 25mg/kg group, the expression of COX-2 in transplanted tumors decreased orderly.7 The effect of aspirin on angiogenesis of ovarian carcinoma: The expression of VEGF in transplanted tumors decreased orderly in five groups including of control group, aspirin 15mg/kg group, aspirin 25mg/kg group, aspirin plus CTX group and CTX group. It was MVD of each group that showed in control group was 19.4±2.9, in aspirin 15mg/kg group was 13.1±1.8, in aspirin 25mg/kg group was 12.3±1.1, in aspirin plus CTX group was 7.2±2.2, in CTX group was 9.1±3.4. MVD in each therapy group was lower than that in control group(P<0.05). It was no significantly for the therapy group to compare with each other random(P>0.05).Conclusions:The study revealed that aspirin could inhibit the growth of human ovarian carcinoma SKOV3 transplanted subcutaneously in nude mice and lead to cellular apoptosis . The mechanism of aspirin on anticancer may be that decreased the expression of COX-2 in tumor tissue. There had positive relation between the expression of COX-2 and angiogenesis related factor. Antiangiogenesis may be one of mechanisms by which aspirin exerted its tumor chemopreventive and therapeutic effects. Treatment with aspirin is a potentially useful anticancer or therapy for ovarian carcinoma.