| Objective: to study the inhibition, sensitization and reversing PTX drug resistanceeffect of β-elemene to human ovarian cancer cell line A2780and drug-resistant cell lineA2780/PTX, and explore its possible mechanism.Method:1. this experiment explored the effect of the experimental group withdifferent concentrations (1.25ug/ml,2.5ug/ml and5ug/ml,10ug/ml,20ug/ml,40ug/ml,80ug/ml,160ug/ml,320ug/ml,640ug/ml) of β-elemene diluted with DMEM_H medium onhuman ovarian cancer cell lines A2780and its drug resistance cell line A2780/PTX, MTTmethod is used to measure the growth inhibition rate of β-elemene.2. this experimentexplored the role of the experimental group with different concentrations of paclitaxel(0.5ng/ml,1ng/ml,2ng/ml,4ng/ml,8ng/ml,16ng/ml,32ng/ml,64ng/ml,128ng/ml,256ng/ml), alone and/or in combination with low toxicity dose β-elemene(30ug/ml) inovarian cancer cell lines A2780and its drug resistant cell lines A2780/PTX, MTT methodis used to detect its sensitization effect.3this experiment explored the effect of theexperimental group with different concentrations of paclitaxel, β-elemene, alone and/orcombination in drug resistance cell line A2780/PTX, the cell cycle was measured by flowcytometry.4. Western blot method to detect the expression of P-gp, XIAP and survivinggene with50ug/ml β-elemene,10ng/ml PTX and combination in A2780/PTX cells.Results:1. The results of β-elemene role in ovarian cancer cell line A2780and drug-resistantcell line A2780/PTX show that it can inhibit the growth of ovarian cancer cell A2780andresistant strains.The IC50is76.96ug/ml（A278024h）,100.7ug/ml（A2780/PTX24h）,53.06ug/ml（A278048h） and57.27ug/ml（A2780/PTX48h）, respectively.2. The results of paclitaxel alone or in combination with low toxicity doseβ-elemene(30ug/ml) in ovarian cancer cell lines A2780and drug-resistant cell line A2780/PTX, the IC50is6.027ng/ml（A2780+PTX）,2.72ng/ml（A2780+PTX+ELE）,44.98ng/ml（A2780/PTX+PTX）and10.25ng/ml（A2780/PTX+PTX+ELE）, respectively.The IC50of drug resistant cell lines is7.46times that of sensitive strains with PTX rolealone; when combining β-elemene, IC50of drug resistant cell lines is3.77times that ofsensitive strains, fell by twice; IC50of sensitive strains with PTX alone is2.22times ofcombination, while the IC50of resistant strains is4.39times of combination.3. β-elemene(20ug/ml,50ug/ml) and PTX(5ng/ml,10ng/ml) alone can riseA2780/PTX cells in G2/M phase with a significant proportion, and with the doses werepositively correlated, while β-elemene in combination with PTX significantly make cellsaccumulate in G2/M phase.4.50ug/ml β-elemene alone or with10ng/ml PTX treatment can obviouslydown-regulate the expression of P-gp, XIAP and survivin in A2780/PTX cells, but nosignificant change found in PTX alone.Conclusion:1. β-elemene has obvious inhibitory effect on ovarian cancer cell lines A2780anddrug-resistant cell line A2780/PTX, and its inhibition effect has a dose and time dependent.2It has different degree of sensitization effect on ovarian cancer cell lines A2780anddrug-resistant cell line A2780/PTX with PTX in combination with low cytotoxicityconcentrations β-elemene, and the stronger effect on A2780/PTX. It indicate thatβ-elemene can significantly reverse multidrug resistance of PTX.3. β-elemene and PTX alone or combination can make the cell blocks in G2/M phase,two kinds of drugs used in combination with positive synergy, induced cells moreaccumulated in the G2/M phase.4. β-elemene and PTX alone or in combination can significantly down-regulate theexpression of P-gp, XIAP and survivin, β-elemene increasing PTX sensitization andreversing drug resistance mechanism of anti-tumor cells may be decrease the expression ofthe drug resistance related gene P-gp, XIAP and survivin. |
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