| Objective:Ovarian cancer is one of the most common malignant tumors in the gynecologic tumor. The mortality of ovarian cancer is the highest among all the gynecologic tumors. Because of its indistinct clinical symptoms, we can not make a diagnosis during the early stage. So the patients with ovarian cancer are poor prognosis. Although traditional treatments make a progress, the prognosis of ovarian cancer is remain poor. Study have approved that angiogenesis plays a key role in the development and metastacis of solide tumor, and angiogenesis maybe correlated with ascite formation in ovarian cancer. Tumor and host also can produce many angiogenesis factors, which act on each other and play a role in all process of tumorigenesis. VEGF is by far the most important factor that elicits the angiogenesis. VEGF (vascular endothelial growth factor), through the binding with VEGF receptor, induce a series of reaction. Now, chemo- therapy is still one of the most important therapeutic tools beside operation. Studies discovered that one of the reasons to induce the failure of chemotherapy is tumor's multidrug resistance to drugs. Multidrug resistance is, induced by a kind of drug, while resistance to this drug, intersect drug fast to another drug which is independent in structure and mechanism of action. P-gp(P-glycoprotein) that encoded by MDR1 gene(multidrug resistance gene 1), can pumps multiple types of drugs out of the cell using the energy generated from ATP, and confers multidrug resistance on cancer cells. This article is to investigate the effects of OCT (octreotide) on the proliferation of human ovarian cancer SKOV3 cells. Moreover, to check the effects of OCT combined with DDP on human ovarian cancer SKOV3 cells, and to analyze the mechanisms of inhibiting the prolifer- ation in blood vessel and drug resistance, to probe the feasibility of OCT in clinical therapy.Methods:1 Cells cultivated of SKOV3 and mensurated the cell growth curve.2 Human ovarian cancer SKOV3 cells were incubated with different concentration of octreotide in vitro. The cytotoxic effect of octreotide on the proliferation of SKOV3 cells was measured by MTT colorimetric method.3 MTT colorimetric method was performed to evaluate the effect of octreotide combined with DDP to SKOV3 cells. Jin's formula was performed to determine whether the combination of octreotide with DDP could result in a synergistic effect or not. More than 0.85 of the interaction index was thought to be as a synergic effect, while less than 0.85 was thought to be as antagonism. 4 Observe the morphology of cell with light microscope and H-E staining.5 The expression level of VEGF and P-glycoprotein on SKOV3 cells before and after octreotide treatment, measured by the method of immunohistochemistry.6 The effect of OCT on the migration of SKOV3 cells.Results:1 SKOV3 cells growth fast, but cell growths relatively slowly when add octreotide in and with the increasing of concentration the cell growth change more gently.2 The proliferation of SKOV3 cells could be inhibited by the different concentrations of octreotide (0.1, 0.5, 1, 5, 10μg/mL). With the increasing concentration of octreotide, the cytotoxic effects were enhanced. Furthermore, with the prolong- ed treatment time, the cytotoxic effects were also enhanced, and there was a significant difference between the treatment group and the control group (P<0.05), which means octreotide could inhibit the proliferation of SKOV3 cells significantly and this inhibition was dose-dependent and time-dependent.3 Octreotide combined with DDP could inhibit the prolifer- ation of SKOV3 cells. The results showed that octreotide (0.5, 1, 5μg/mL) combined with DDP induced synergic cytotoxic effects to SKOV3 cells, and the synergic effects which further be testified by interaction index from Jin's formula could enhanced with the increasing octreotide.4 When treated with octreotide, SKOV3 cells changed significantly in morphology observed by light microscopy. SKOV3 cells untreated with octreotide were fusiform, diamond, and they were satiation; while the cells treated with octreotide were shrinked and broken, became irregular in shape. Morphological changes of SKOV3 cells of H-E staining were further observed by light microscopy, SKOV3 cells untreated with octreotide were fusiform, diamond, and they were satiation, furthermore, the cell nucleus staining were uniform and clear. But SKOV3 cells treated with octreotide became rounding, the volume was minified, the cell kytoplasm was concentrated, there were also the staining cell nucleus uneven phenomenon.5 The effect of ICC: Positive reaction of VEGF were detected almost in cytoplasm, took on brown-yellow. The cells untreated with octreotide could be stained into stronger positive. The expression of VEGF in SKOV3 cells treated with octreotide in 1μg/ml for 48 hours was weaker than that in untreated cells, and the difference was significant (P<0.05). Furthermore, the expression of VEGF decreased along with the increase of drug concentration (P<0.05). There was positive expression of P-gp in cytoplasm and plasmalemma of untreated SKOV3 cells. After being treated with octreotide, the expression became lower and lower along with the increase of drug concentration (P<0.05).6 Pretreated with octreotide for 24h, the invasive number of SKOV3 cells under microscope (×400) were 82 and 35 respectively obviously decreased in contrast with control (146). Conclusions:1 Octreotide can inhibite the proliferation of human ovar- ian cancer SKOV3 cel1s in vitro, which provided some theoretical foundation for the clinical use of octreotide.2 Octreotide induced the cytotoxic effects to SKOV3 cells in a dose and time dependent manner in vitro in some determinate concentration.3 Combination of OCT and DDP enhance the effect, inhibition ratio is higher than DDP and OCT alone in vitro. Possess the synergistic effect.4 Octreotide can down regulation the expression of VEGF protein to SKOV3 cells. To illustrate the effect of anti-tumor may have some relationship with the inhibition of vasifor- mation.5 Octreotide can down regulation the expression of P-gp to SKOV3 cells. It maybe has some relationship with the drug tolerance.6 Inhibition effect of OCT on SKOV3 cells was in a dose-dependent and time-dependent maner, OCT can degrade the migration of SKOV3 cells.
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