Etoposide is widely used for cancer chemotherapy in the clinic.However,long-term etoposide treatment can lead to adverse effects or drug resistance.To improve the situation,we evaluated the therapeutic efficiency of e...Etoposide is widely used for cancer chemotherapy in the clinic.However,long-term etoposide treatment can lead to adverse effects or drug resistance.To improve the situation,we evaluated the therapeutic efficiency of etoposide combined with inhibitors of bromodomain and extraterminal(BET)family proteins,which have recently emerged as novel anti-cancer targets due to their critical roles in cancer development.Firstly,we showed BRD4,one of the main targets of BET inhibitors,was involved in DNA damage response(DDR)via the homologous recombination(HR)repair pathway.展开更多
Dear Editor,Chromatin modifications regulate multiple cellular progressions(Bannister and Kouzarides,2011;Zhang et al.,2021).Numerous histone modifications and their correspondent enzymes have been identified in the p...Dear Editor,Chromatin modifications regulate multiple cellular progressions(Bannister and Kouzarides,2011;Zhang et al.,2021).Numerous histone modifications and their correspondent enzymes have been identified in the past decades(Huang et al.,2014)and more histone modification sites and types have been gradually identified in recent years(Kim et al.,2019;Lu et al.,2019).展开更多
Photothermal therapy(PTT)induces thermoresistance through cellular heat shock response,which impairs the therapeutic efficacy of the PTT.To resolve this problem,we developed a photothermal theranostics(denoted as PMH)...Photothermal therapy(PTT)induces thermoresistance through cellular heat shock response,which impairs the therapeutic efficacy of the PTT.To resolve this problem,we developed a photothermal theranostics(denoted as PMH),which integrated the photothermal conversion agent of PdMo bimetallene with histone deacetylase 6(HDAC6)selected inhibitor(ACY-1215),showing the synergistic antitumor effect both in vitro and in vivo.Mechanistically,under the photoacoustic imaging(PA)navigation,the released ACY-1215 triggered by NIR laser irradiation decrease the heat shock proteins(HSPs)expression and weaken the HDAC6-regulated HSP90 deacetylation,thus hindering the degradation of PTT-induced misfolded or unfold proteins through proteasome dependent pathway.Moreover,mild photothermal therapy(mPTT)treatment compromised the autophagy,which induced by HDAC6 inhibition,leading to mPTTinduced misfolded or unfold proteins further accumulation.Given that inhibition of HDAC6 plus m PTT contribute to tumor eradication.This study develops a promising combination strategy based on m PTT for future cancer treatment.展开更多
基金supported by the National Key R&D Program of China(No.2017YFA0503900)the National Natural Science Foundation of China(No.32090033,81720108027,81530074,82103275,82002986)+3 种基金the Science and Technology Program of Guangdong Province in China(No.2017B030301016)China Postdoctoral Science Foundation(No.2019M663092)Basic and Applied Basic Research Foundation of Guangdong Province(No.2019A1515110039,2019A1515110041,2021A1515011126)Shenzhen Municipal Commission of Science and Technology Innovation(China)(No.JCYJ20170818092450901,JCYJ20200109114214463).
文摘Etoposide is widely used for cancer chemotherapy in the clinic.However,long-term etoposide treatment can lead to adverse effects or drug resistance.To improve the situation,we evaluated the therapeutic efficiency of etoposide combined with inhibitors of bromodomain and extraterminal(BET)family proteins,which have recently emerged as novel anti-cancer targets due to their critical roles in cancer development.Firstly,we showed BRD4,one of the main targets of BET inhibitors,was involved in DNA damage response(DDR)via the homologous recombination(HR)repair pathway.
基金supported by the National Natural Science Foundation of China(32090030,81720108027,81530074,82103270)the National Key Research and Development Program of China(2017YFA0503900)+2 种基金Science and Technology Program of Guangdong Province in China(2017B030301016)Shenzhen Municipal Commission of Science and Technology Innovation(JCYJ20170818092450901)China Postdoctoral Science Foundation(2018M643191)。
文摘Dear Editor,Chromatin modifications regulate multiple cellular progressions(Bannister and Kouzarides,2011;Zhang et al.,2021).Numerous histone modifications and their correspondent enzymes have been identified in the past decades(Huang et al.,2014)and more histone modification sites and types have been gradually identified in recent years(Kim et al.,2019;Lu et al.,2019).
基金financially supported by National Key R&D Program of China(Nos.2020YFA0908800,2018YFA0704000)Basic Research Program of Shenzhen(Nos.JCYJ20200109105620482,JCYJ20180507182413022)Shenzhen Science and Technology Program(No.KQTD20190929172538530)。
文摘Photothermal therapy(PTT)induces thermoresistance through cellular heat shock response,which impairs the therapeutic efficacy of the PTT.To resolve this problem,we developed a photothermal theranostics(denoted as PMH),which integrated the photothermal conversion agent of PdMo bimetallene with histone deacetylase 6(HDAC6)selected inhibitor(ACY-1215),showing the synergistic antitumor effect both in vitro and in vivo.Mechanistically,under the photoacoustic imaging(PA)navigation,the released ACY-1215 triggered by NIR laser irradiation decrease the heat shock proteins(HSPs)expression and weaken the HDAC6-regulated HSP90 deacetylation,thus hindering the degradation of PTT-induced misfolded or unfold proteins through proteasome dependent pathway.Moreover,mild photothermal therapy(mPTT)treatment compromised the autophagy,which induced by HDAC6 inhibition,leading to mPTTinduced misfolded or unfold proteins further accumulation.Given that inhibition of HDAC6 plus m PTT contribute to tumor eradication.This study develops a promising combination strategy based on m PTT for future cancer treatment.
