3-acetyl-11-keto-beta-boswellic acid decreases the malignancy of taxol resistant human ovarian cancer by inhibiting multidrug resistance (MDR) proteins function

Abstract

ObjectiveRecurrence of ovarian cancer is mainly due to multidrug resistance (MDR). 3-acetyl-11-keto-beta-boswellic acid (AKBA) could reverse the multidrug resistance in human ileocecal adenocarcinoma cells, but whether AKBA could modulate acquired MDR in ovarian cancer needs to be elucidated. MethodsThe current study examined the effect of AKBA on ovarian cancer MDR using a Taxol resistant human ovarian cancer cell line A2780/Taxol. Cell proliferation, migration and invasion, the intracellular accumulation of Rhodamine 123 and expression of MDR proteins were studiedin vitro. Furthermore, the effect of AKBA on oncogenicity of A2780/Taxol cells in nude mice xenograft model was studied. ResultsThe results showed that apart from its cytostatic and apoptosis-induction effect, AKBA could restrain A2780/Taxol cell migration and invasion. In addition, AKBA improved the sensitivity of A2780/Taxol cells to Taxol apparently, and the reversal of MDR by AKBA was evident by increasing intracellular Rhodamine 123 in cells. Furthermore, the anti-cancer potential of AKBA was evidenced as that AKBA treatment significantly slowed tumor growth and decreased the expression of P-gp, LRP, BCRP and MRP. ConclusionAbove results indicated that AKBA might be a potential compound to reverse MDR in human ovarian cancer.