NSC 23925

Cell experiment:

To determine whether NSC23925 can prevent the emergence of paclitaxel resistance, paclitaxel resistant ovarian cancer cells are used. In brief, 1×105 SKOV-3 cells are suspended in culture media containing paclitaxel alone, 1 μM NSC23925 alone, or paclitaxel in combination with 1 μM NSC23925. When the cells are cultured to 90% confluence, 1×105 cells are reseeded in a new tissue culture flask, and the paclitaxel dose is increased stepwise. The initial concentration of paclitaxel is 0.0001 μM. At different selection points cell sublines are collected and stored at liquid nitrogen for further analysis[1].

Animal experiment:

Nude female mice at approximately 3 to 4 weeks of age are used. To evaluate the effects of NSC23925 on the induction of paclitaxel resistance in vivo, the paclitaxel resistant cells are established in human ovarian cancer xenograft models. Briefly, on day 1, approximately 2×106 parental sensitive SKOV-3 cells are injected subcutaneously with Matrigel into the flanks of 3 to 4-week-old female nude mice. Administration is initiated 12 days after injection of tumor cells. The mice are randomized into 4 groups and treated intraperitoneally with either saline alone, NSC23925 alone (50 mg/kg), paclitaxel (25 mg/kg) alone, or paclitaxel (25 mg/kg) in combination with NSC23925 (50 mg/kg) twice per week for 3 weeks followed by a treatment-free interval of 2 weeks. The second round of treatment is then continued. The size of tumors is recorded twice a week beginning on day 13. Tumor volume is measured with a digital caliper and calculated according to the formula (length×width2)/2[1].

References:

[1]. Yang X, et al. Nsc23925 prevents the development of paclitaxel resistance by inhibiting the introduction of P-glycoprotein and enhancing apoptosis. Int J Cancer. 2015 Oct 15;137(8):2029-39.
[2]. Duan Z, et al. NSC23925, identified in a high-throughput cell-based screen, reverses multidrug resistance. PLoS One. 2009 Oct 12;4(10):e7415.