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

        Zhengbo Hu,Lugen Li,Wenxing Lan,Xiao Wei,Xiangyuan Wen,Penghuan Wu,Xianliao Zhang,Xinhua Xi,Yufa Li,Liqi Wu,Wenhu Li,Xiaohong Liao 대한암학회 2022 Cancer Research and Treatment Vol.54 No.1

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

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        Photocatalytic Degradation of Rhodamine B via Fe-g-C3N4 Activated Sulfate Radical-Based Advanced Oxidation Processes and the Synergistic Mechanism

        Zhan Xinyuan,She Zhixiang,Yue Zhengbo,Hu Fupeng,Wang Guangcheng,Wang Shaoping,Li Wei,Liu Bing,Wang Jin 한국화학공학회 2024 Korean Journal of Chemical Engineering Vol.41 No.1

        Fe-doped g-C 3 N 4 has been proven to have the potential of visible light photocatalysis, but its catalytic activity of peroxymonosulfate (PMS) is neglected. Herein, the complex advanced oxidation processes of Fe-g-C 3 N 4 mediated PMS and visible light photocatalysis was developed, named as Vis/Fe-g-C 3 N 4 /PMS system, whose eff ects and synergistic mechanism for decomposing Rhodamine B (RhB) was evaluated. The coupling of sulfate radicals and photocatalysis for RhB degradation showed that the synergistic effi ciency ( η Syn ) and factor ( S c ) were 20.1% and 4.82, respectively, with a degradation effi ciency of 99.8%. Iron species dispersed on g-C 3 N 4 provided active sites for PMS activation to generate sulfate radicals, simultaneously reduced the forbidden band, and separated the photo-generated charges of g-C 3 N 4 . h + , SO 4 · ‾ and 1 O 2 were the main active species, and the increase of 1 O 2 was the cause of the synergistic eff ect. The possible degradation path of RhB by this coupling system was proposed. Our fi ndings prove that Vis/Fe-g-C 3 N 4 /PMS system has a great potential to decompose dye wastewater, and also to be an environmental remediation perspective.

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