Arsenic Trioxide Combined With Hedgehog (Hh) Signal Pathway Antagonists Cyclopamine On Non-Male Influences On Growth Of Transplanted Tumor Of Prostate Cancer

Objective：Study of arsenic trioxide （As₂O₃） combined with Hedgehog （Hh） signalpathway antagonists (Cyclopamine effect on the growth of prostate cancer than maledependence.Methods：The first application of four tetrazolium （MTT） assay of arsenic trioxidecombined with Hedgehog （Hh） signal pathway antagonists (Cyclopamine （cyclopamine）on prostate tumor cells （PC-3） inhibit the proliferation. Flow cytometry was used todetect the apoptosis of tumor cells after administration to. And growth was observedafter administration of tumor through the construction of in vitro tumor sphere model,simulation after administration of drugs in vivo inhibition on tumor growth. Secondly,establish the androgen independent prostate cancer xenograft model in nude mice, wererandomly divided into control group （group A）, arsenic trioxide （As₂O₃） treatmentgroup （group B）, Cyclopamine （cyclopamine） group （group C）, arsenic trioxide （As₂O₃）agent+Cyclopamine （cyclopamine） group （group D） respectively. Every day withphysiological saline, set the concentration of arsenic trioxide （As₂O₃）, Cyclopamine（cyclopamine）, arsenic trioxide （As₂O₃）+Cyclopamine （cyclopamine） injection in nudemice intraperitoneal, survival was observed in nude mice, measured every three days a tumor volume size, to be nude mice after the death of tumor tissue, blood, do thefollowing:1the blood alanine aminotransferase （ALT）, aspartate aminotransferase（AST）, creatinine （Cr） affect the test understanding drug on liver and renal function;2Statistical tumor volume changes;3, nude mice to calculate the median survival timeafter administration of.Results: The experimental results show that, arsenic trioxide （As₂O₃） andHedgehog （Hh） signal pathway antagonists Cyclopamine （cyclopamine） combinedapplication can inhibit tumor cell proliferation is very good. The experiment showedthat tumor spheres, inhibitory effect of combined medication has better ball for tumorgrowth. Nude mice liver and kidney index were investigated, results showed that afteradministration, including three oxidation two arsenical administered group on hepaticand renal effects of maximum. The size of tumor in different administration group.Inhibition of tumor drug combination can better growth. The median survival time ofdifferent drug group was18days in group A, group B, group C25days,27days,38days in group D.Conclusion： Arsenic trioxide （As₂O₃） and Hedgehog （Hh） signal pathwayantagonists Cyclopamine markedly inhibited non androgen dependent prostate cancerxenograft growth. Arsenic trioxide has great toxicity effect on tumor-bearing mice. Thecombination of the two, can play a synergistic effect, achieve more effective antitumoreffect in small doses, achieve the reduction efficiency.