br Results The results showed that apart from its cytostatic
Results: The 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 EPZ031686 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.
Conclusion: Above results indicated that AKBA might be a potential compound to reverse MDR in human ovarian cancer.
Ovarian cancer is the fifth leading cause of cancer death among women and the most lethal gynecologic malignancy . Its high mor-tality rate is mainly due to late diagnosis for lacking early stage signs and symptoms. Approximately 70% of patients are diagnosed at ad-vanced stage, and the 5-year survival rate is less than 30% . Therapies in treating metastatic ovarian cancer become increasingly ineﬀective .
Debulking surgery followed by platinum/paclitaxel-based che-motherapy is commonly an eﬀective treatment for most ovarian cancer patients. But a majority of them will suﬀer from cancer relapse with chemoresistance, resulting in treatment failure and over 90% of death rate, subsequently . Thus, establishing and using taxol-resistant ovarian cancer cell lines to screen promising chemotherapeutic drugs and elucidating the underlying molecular mechanisms of them are
crucial for the development of eﬀective therapies of ovarian cancer. Recurrence of ovarian cancer is mainly due to multidrug resistance
(MDR). Living cells can achieve MDR via the active eﬄux of a broad range of anticancer drugs through cellular membrane by MDR proteins. As reported previously, the ATP binding cassette (ABC) transporters P-glycoprotein (P-gp), multidrug resistance associated protein (MRP), breast cancer resistance protein (BCRP)  together with lung re-sistance-related protein (LRP) are responsible for the uptake and eﬄux of a multitude of substances from cancer cells . In ovarian cancer, P-gp has been comprehensively studied and is responsible for reducing intracellular concentration of paclitaxel [4,7].
The genus Boswellia is applied widely as a traditional remedy for various ailments clinically [8,9]. Boswellic acid is a pentacyclic tri-terpene acid extracted from the Indian frankincense Boswellia serrata. There are mainly four pentacyclic triterpene acids in plant extract of Boswellia serrata including 3-acetyl-11-keto-beta-boswellic acid (AKBA),
E-mail addresses: [email protected] (Z. Buluan), [email protected] (W. Jinhua). 1 These authors have contributed equally to this work.
Fig. 1. AKBA enhances the chemotherapeutic response of Taxol and recovers the accumulation of rhodamine 123 in A2780/Taxol cells. (A–C) Eﬀect of AKBA and taxol on A2780/taxol cell viability was determined by CCK-8 assay. Cells were exposed to taxol and/or AKBA for 72 h, cell viability was analyzed and IC50 values were calculated. (Mean ± SD, n = 6). (D) Growth curve of A2780/T with AKBA and taxol treatment was analyzed in 5 consecutive days. In 5th day, cells were incubated with CCK8 solution, and the absorbance at 450 nm was recorded (Mean ± SD, n = 3, *P < 0.05, **P < 0.01 versus A2780/Taxol). (E) Eﬀect of AKBA on accumulation of intracellular Rhodamine 123 in A2780/Taxol. A2780/Taxol cells were treated with 12.5 μM AKBA for 72 h and incubated for another 2 h with rhodamine 123. A2780 cells were used as the parent control cells. Rhodamine 123 fluorescene intensity was analyzed by flow cytometry (Mean ± SD, n = 3,