Abstract:

Objective   To investigate the effect and mechanism of deacetyl-mycoepoxydiene (DM) on reversing resistance to taxol in tumor cells. Methods   MTT colorimetric assay was employed to evaluate the cytotoxicity of DM to sensitive tumor cells A549 and drug resistant cells A549/T. The influence of DM on cellular taxol sensitivity was analyzed as well. The reversal fold was approximated by MTT, and the apoptotic percentage was estimated in AnnexinV method. The accumulation of Rh123 in drug-resistance cells was observed by flow cell cytometry (FCM). Additionally, the content of taxol and the expression of Ⅲ-β-tubulin protein were respectively quantified by high performance liquid chromatography (HPLC) and Western blotting. Results   This study demonstrated that DM enhanced the cellular taxol sensitivity and thus increased the apoptotic percentage of taxol-resistant tumor cells. The content of taxol and Rh123 was greatly increased in DM-treated A549/T cells. Moreover,Western blotting results showed that DM inhibited the expression of Ⅲ-β-tubulin protein in A549/T cells. Conclusion   DM can effectively reverse the multidrug resistance and increase the drug sensitivity of tumor cells, which may function by interfering the expression of Ⅲ-β-tubulin protien and/or inhibiting the drug-resistant P-glyco-protein-mediated efflux pump on the cell membrane.

Key words: Deacetyl-mycoepoxydiene； Taxol； Tumor cells； Multidrug resistance; A549