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. 2019 Jun 19;6(4):419–430. doi: 10.1016/j.gendis.2019.06.001

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© 2019 Chongqing Medical University. Production and hosting by Elsevier B.V.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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Low MDM2 expression blocks the inhibitory effects of SP141 in HCC PDX models. HMP412 (MDM2^high) and HMP431 (MDM2^low) tumor tissues from patients were implanted into the right flanks of male NOD/SCID mice. After the tumors had grown through three subsequent cycles of excision, fragmentation, and transplantation in new mice, SP141 was administered by i.p. injection at a dose of 40 mg/kg/d, 5 d/wk for 4 weeks. The tumor size was monitored every 4 days in both the HMP412 (MDM2^high) (A) and HMP431 (MDM2^low) (B) models. The mice were monitored for changes in body weight as a surrogate marker for toxicity in the HMP412 (MDM2^high) (C) and HMP431 (MDM2^low) (D) models. At the termination of the experiments, the HMP412 (E) and HMP431 (F) tumors were removed and analyzed for the protein expression of MDM2 by immunohistochemistry (scale bar, 20 μm). Representative images are shown.