Enrichment of Wee1/CDC2 and NF-κB Signaling Pathway Constituents Mutually Contributes to CDDP Resistance in Human Osteosarcoma

• DOI: 10.4143/crt.2021.320
• Publication Date: 2021-05-11T03:10:05Z
• Authors: Zhengbo Hu; Lugen Li; Wenxing Lan; Xiao Wei; Xiangyuan Wen; Penghuan Wu; Xianliao Zhang; Xinhua Xi; Yufa Li; Liqi Wu; Wenhu Li; Xiaohong Liao
• Keywords: Wee1; Survivin

Osteosarcoma (OS) universally exhibits heterogeneity and cisplatin (CDDP) resistance. Although the Wee1/CDC2 nuclear factor кB (NF-κB) pathways were reported to show abnormal activation in some tumor cells with CDDP resistance, whether there is any concrete connection currently unclear. We explored it human OS cells.Multiple cell lines exposed a Wee1 inhibitor (AZD1775) assess half-maximal inhibitory concentration values. Western blot, coimmunoprecipitation, confocal immunofluorescence, cycle, Cell Counting Kit-8assays performed explore between NF-κB their subsequent physiological contribution Finally, CDDP-resistant PDX-OS xenograft models established confirm that AZD1775 restores antitumor effects of CDDP.A sensitivity hierarchy exists. In highly CDDP-tolerant lines, RelA physically crosslinked, which resulted increased abundance phosphorylated CDC2 (Y15) (S536) consequent modulation cycle progression, survival, proliferation. inhibition restored on these processes cells. addition, animal experiments showed combined not only efficacy but also amplified inhibiting growth prolonged median survival mice.Simultaneous enrichment molecules coactivation new molecular mechanism resistance this signature may respond well as an alternative treatment strategy.