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Paclitaxel (Taxol) is currently used as the front-line chemotherapeutic agent for several cancers including ovarian carcinoma; however, the drug frequently induces drug resistance through multiple mechanisms. The new strategy of using natural compounds in combination therapies is highly attractive because those compounds may enhance the efficacy of chemotherapy. In this study, we found that tectorigenin, an isoflavonoid isolated from flower of Pueraria thunbergiana, enhanced the growth-inhibitory effect of paclitaxel in paclitaxel-resistant ovarian cancer cells (MPSC1(TR), A2780(TR) and SKOV3(TR)) as well as their naive counterparts. The combination of tectorigenin with paclitaxel resulted in a synergistic apoptosis compared with either agent alone through activation of caspases-3, -8 and -9. Treatment with tectorigenin inhibited the nuclear translocation of NFκB and the expression of NFκB-dependent genes such as FLIP, XIAP, Bcl-2, Bcl-xL and COX-2, which are known to be associated with chemoresistance. In addition, the tectorigenin-paclitaxel combination inhibited the phosphorylation of IκB and IKK and the activation of Akt in paclitaxel-resistant cancer cells. Moreover, tectorigenin-paclitaxel-induced cell growth inhibition was enhanced by pretreatment with the Akt inhibitor LY294002 or overexpression of the dominant negative Akt (Akt-DN), but reduced by overexpression of constitutively activated Akt (Akt-Myr). Furthermore, we found that Akt-Myr, at least in part, reversed tectorigenin-paclitaxel-induced nuclear translocation of NFκB and the phosphorylation of IκB and IKK. These data suggest that tectorigenin could sensitize paclitaxel-resistant human ovarian cancer cells through inactivation of the Akt/IKK/IκB/NFκB signaling pathway, and promise a new intervention to chemosensitize paclitaxel-induced cytotoxicity in ovarian cancer.

This paper proposes a new two-dimensional (2D) actuation method for a microrobot that uses a stationary two-pair coil system. The coil system actuates the microrobot by controlling the magnitude and direction of the external magnetic flux. The actuation of the microrobot consists of an alignment to the desired direction and a linear movement of the microrobot by non-contact electromagnetic actuation. Firstly, the actuation mechanism of the stationary coil system is theoretically derived and analyzed. Secondly, the tendency of the magnetic flux in the coil system are analyzed and compared by preliminary theoretical analysis. Through various locomotive experiments of the microrobot, the performance of the electromagnetic actuation by the proposed stationary two-pair coil system is evaluated. Using the proposed 2D actuation method, the microrobot is aligned to the desired direction by Helmholtz coils and is driven to the aligned direction by Maxwell coils. By the successive current control of the coil system, the microrobot can move along a desired path, such as a rectangular-shaped or a diamond-shaped path.