Non-protein coding RNAs have emerged as a regulator of cell signaling and cancer progression through regulation of cell proliferation,metastatic burden,and cancer stem cell capacity.A subtype of non-protein coding RNA...Non-protein coding RNAs have emerged as a regulator of cell signaling and cancer progression through regulation of cell proliferation,metastatic burden,and cancer stem cell capacity.A subtype of non-protein coding RNA is long non-protein coding RNA(lncRNA).Besides their aforementioned roles in cancer cell biology,dysregulation of lncRNAs contribute to resistance to therapeutic treatments.A couple of important therapeutic classes are chemotherapy and targeted/hormone therapies.This review highlights the variety of malignancies affected by lncRNA dysregulation and the underlying mechanism causing therapeutic resistance.展开更多
Drug resistance presents one of the major causes for the failure of cancer chemotherapy.Cancer stem-like cells(CSCs),a population of self-renewal cells with high tumorigenicity and innate chemoresistance,can survive c...Drug resistance presents one of the major causes for the failure of cancer chemotherapy.Cancer stem-like cells(CSCs),a population of self-renewal cells with high tumorigenicity and innate chemoresistance,can survive conventional chemotherapy and generate increased resistance.Here,we develop a lipid-polymer hybrid nanoparticle for co-delivery and cell-distinct release of the differentiation-inducing agent,all-trans retinoic acid and the chemotherapeutic drug,doxorubicin to overcome the CSC-associated chemoresistance.The hybrid nanoparticles achieve differential release of the combined drugs in the CSCs and bulk tumor cells by responding to their specific intracellular signal variation.In the hypoxic CSCs,ATRA is released to induce differentiation of the CSCs,and in the differentiating CSCs with decreased chemoresistance,DOX is released upon elevation of reactive oxygen species to cause subsequent cell death.In the bulk tumor cells,the drugs are released synchronously upon the hypoxic and oxidative conditions to exert potent anticancer effect.This cell-distinct drug release enhances the synergistic therapeutic efficacy of ATRA and DOX with different anticancer mechanism.We show that treatment with the hybrid nanoparticle efficiently inhibit the tumor growth and metastasis of the CSC-enriched triple negative breast cancer in the mouse models.展开更多
基金This work was supported by Baylor College of Medicine Comprehensive Cancer Training Program(CPRIT RP160283).
文摘Non-protein coding RNAs have emerged as a regulator of cell signaling and cancer progression through regulation of cell proliferation,metastatic burden,and cancer stem cell capacity.A subtype of non-protein coding RNA is long non-protein coding RNA(lncRNA).Besides their aforementioned roles in cancer cell biology,dysregulation of lncRNAs contribute to resistance to therapeutic treatments.A couple of important therapeutic classes are chemotherapy and targeted/hormone therapies.This review highlights the variety of malignancies affected by lncRNA dysregulation and the underlying mechanism causing therapeutic resistance.
基金supported by the National Natural Science Foundation of China(82273876,81971730,81673381,82104090)the Fok Ying-Tong Education Foundation for Young Teachers in the Higher Education Institutions of China(171028)+2 种基金the Project of State Key Laboratory of Natural Medicines of China Pharmaceutical University(SKLNMZZ202024,China)the Natural Science Foundation of Jiangsu Province(BK20210425,China)the Postdoctoral Research Funding of Jiangsu Province(2021K051A,China).
文摘Drug resistance presents one of the major causes for the failure of cancer chemotherapy.Cancer stem-like cells(CSCs),a population of self-renewal cells with high tumorigenicity and innate chemoresistance,can survive conventional chemotherapy and generate increased resistance.Here,we develop a lipid-polymer hybrid nanoparticle for co-delivery and cell-distinct release of the differentiation-inducing agent,all-trans retinoic acid and the chemotherapeutic drug,doxorubicin to overcome the CSC-associated chemoresistance.The hybrid nanoparticles achieve differential release of the combined drugs in the CSCs and bulk tumor cells by responding to their specific intracellular signal variation.In the hypoxic CSCs,ATRA is released to induce differentiation of the CSCs,and in the differentiating CSCs with decreased chemoresistance,DOX is released upon elevation of reactive oxygen species to cause subsequent cell death.In the bulk tumor cells,the drugs are released synchronously upon the hypoxic and oxidative conditions to exert potent anticancer effect.This cell-distinct drug release enhances the synergistic therapeutic efficacy of ATRA and DOX with different anticancer mechanism.We show that treatment with the hybrid nanoparticle efficiently inhibit the tumor growth and metastasis of the CSC-enriched triple negative breast cancer in the mouse models.
