Research Of Isocorydine On Human Cervical Cancer(SiHa) Transplantation Tumor In Nude Mice

Background: Cervical cancer(cc) is the second most common cancer for the Chinese women, who creates the woman health harm is only inferior to breast cancer. Recently, searching for the traditional Chinese medicine that can inhibit tumor growth, induce tumor cells apoptosis, cause cell-cycle arrest, and suppress tumor metastasis has been the hottest research spot in the treatment of cervical cancer. Isocorydine(ICD) is a monomer belongs to the isoquinoline alkaloids, which come from one traditional Chinese medicine named Dicranostigma Leptodum or Maxim. ICD has been well characterized to possess extensive pharmacological activities. Studies found that ICD can induce apoptosis of the liver cancer and damage the liver cancer stem cells selectively. While, on cervical cancer there has no literature reports in China or abroad.Objective: On the basis of the vitro experiment, we built a Si Ha transplantation tumor model in BALB/c nude mice to explore the inhibition effect of the different ICD concentration. Meanwhile, compared with the expression levels of p53, HPV16E6, PARP, E-cadherin and Vimentin, to research the possible mechanism and provide an experiment basis for the clinical future development of ICD.Methods: A transplanted tumor model by subcutaneously injecting Si Ha cells which were in logarithmic growth phase into the BALB/c nude mice was established. Mice were randomly assigned into groups by intraperitoneal injection when the tumors average diameters reached 0.5cm. Observe the influenced on the transplanted tumor, calculate the inhibitory rate and the growth inhibition rate. Once the mice were sacrificed, the tumor tissue stained with HE, immunohistochemistry and western blotting were used to detect the expression level of p53, HPV16E6, PARP, E-cadherin and Vimentin.Results: 1. The tumor formation rate of the BALB/c nude mice was 100%. 2. In the process of experiment, all mice weights were increased, and there were no significant difference between the groups. 3. With the increase of the ICD concentration, tumor weight and tumor volume reduced gradually. Statistical significances were found between the ICD(low dose and middle dose) and the PBS negative control group(P<0.05). 4. Immunohistochemistry, Western blotting results showed that compared with the PBS negative control group, p53 and E-cadherin expression enhanced in the ICD groups. While HPV16E6, Vimentin and PARP expression decreased in the ICD groups.Conclusions : 1. ICD had no toxic side effects to the mice weights. 2. ICD can suppress the tumor growth in the Si Ha xenograft medels. 3. The anti-tumor effect of ICD may be correlated with the increases expressions of P53 and decreases expressions of HPV16E6, thus inhibiting cervical cancer Si Ha proliferation. 4. The anti-tumor effect of ICD may be correlated with reverse effect of EMT, which could increase the expression of E-cadherin and decrease the expression of Vimentin.