The Anti Invasion And Migration Effect Of As₂O₃ On MHCC97H And The Preparation Of As₂O₃-PLGA Bio-degeneration Microspheres

Invasion and metastasis is the most prominent obstacles to further improvement of clinical treatment efficacy in hepatocellular carcinoma (HCC). As₂0₃ has apoptosis-inducing effect in many solid tumor cell lines, and MHCC97H is a highly metastatic human hepatocellular carcinoma cell line. Purpose: TO assess the anti-invasion and migration effect of As₂0₃ on MHCC97H cell line. Methods: A wide range concentration of arsenic trioxide were cultured with MHCC97H with different time. We observed the cells change. Cell growth curve, scratch test, Transwell permeable supports were used to assess the anti-invasion and migration effect of As₂O₃ on MHCC97H cell line. RT-PCR test the express of MMP-9 and Timp-1 gene in MHCC97H which treated by different concentration of arsenic trioxide. Result: After culturing with As₂0₃, MHCC97H cell present paste wall cells decrease. Float, vacuolation, deformation, granulation and chromatin condensation were observed. Those appearance were increased with the prolong of time and the concentration of arsenic trioxide increasing. Scratch test show that the cells which can creep out of the line were decreased after cultured with arsenic trioxide. MHCC97H cells were cultured with different concentration of arsenic trioxide in transwell permeable supports, shown the cells which can pass through the pores decreased with the concentration increase. PT-PCR test showed the express of MMP-9 and Timp-1 gene in MHCC97H were decreased with concentration of arsenic trioxide increasing. Conclusion: As₂0₃ can inhabit the invasion and migration of the MHCC97H cell line.Purpose: To investigate the inhibitory effect of As₂03 on angiogenesis , growth and lung metastasis of LCI-D20 hepatocellular carcinoma in nude mice. Method: LCI-D20 tumor tissues were implanted into the livers of nude mice to establish models in present study. 20 nude mice were randomly divided into a treatment group and a control group, and then treated with As203 at a dose of 3mg/kg daily injection through the tail vein, or 0.9% sodium chloride solution (0. lml) as control. Therapy began on the 7 day after operation and continued for 10 consecutive days. A week later the nude mice were were killed. The liver tumor were weighed, microvessel density (MVD) was analyzed in CD34-stained tumor sections, lung metastatic lesions were searched. Results: LCI-D20 tumor implanted into liver successfully. On day 27 after implantation .average tumor volume was 0. 99±0. 45g in the As203 treated group; whereas it was 2.33 ±0. 78g in the control. The difference between two groups was statistically significant. A dramatically decreased microvessel density in tumor tissues was revealed in the As203 -treated mice compared with control tumor tissues 18. 87±3. 02 versus 48. 33±6. 37, P < 0.01). Conclusion: As203 is able to inhibit angiogenesis , growth and lung metastasis of LCID20 hepatocellular carcinoma in nude mice. The growth inhibitory mechanisms of As2O3 may be attributed to antiangiogenesis in this experiment.Purpose: To optimize the preparation of sustained release microspheres of As203 using the biodegradable materials PLGA for interventional radiology therapy. Methods: The orthogonal test design was used to optimize the technology of preparation with good reproducibility. The surface morphology of the microspheres was observed by scanning electron microscope. The mean diameter and the size distribution of microspheres, the drug loading, the incorporation efficiency, the reappearances of pharmaceutical technology, drug release in vitro were examined. Result: the As2O3 PLGA mocrospheres were regular in their morphology. Drug was enveloped in microspheres but not physically mixed with PLGA. The average particle size was 47. 27±0. 836 u m with 91.25% of the microspheres being in the range of 20-100y m; the drug loading was 14. 60±0. 30%. The reappearance of pharmaceutical technology was good. The microspheres were stable for three months at 4"C and room temperature. The in vitro release properties could be expressed by the Weibull quation: InIn(l/(l-F(t)))=1.0214Int-5.1881 r=0.97. Conclusion: The technology of preparation was successful and As2O3-PLGA microspheres showed sighificant sustained release and suitable for interventional radiology therapy.