It is critical to regulate the senescence-associated secretory phenotype(SASP) due to its effect on promoting malignant phenotypes and limiting the efficiency of cancer therapy. In this study, we demonstrated that mar...It is critical to regulate the senescence-associated secretory phenotype(SASP) due to its effect on promoting malignant phenotypes and limiting the efficiency of cancer therapy. In this study, we demonstrated that marchantin M(Mar-M, a naturally occurring bisbibenzyl) suppressed proinflammatory SASP components which were elevated in chemotherapy-resistant cells. Mar-M treatment attenuated the pro-tumorigenic effects of SASP and enhanced survival in drug-resistant mouse models.No toxicity was detected on normal fibroblast cells or in animals following this treatment. Inactivation of transcription factor EB(TFEB) and nuclear factor-k B(NF-k B) by Mar-M significantly accounted for its suppression on the components of SASP. Furthermore, inhibition of SASP by Mar-M contributed to a synergistic effect during co-treatment with doxorubicin to lower toxicity and enhance antitumor efficacy. Thus, chemotherapy-driven pro-inflammatory activity, seen to contribute to drug-resistance, is an important target for Mar-M. By decreasing SASP, Mar-M may be a potential approach to overcome tumor malignancy.展开更多
Dear Editor,Multidrug resistance(MDR)is still a major challenge for successful cancer treatments.Numerous mechanisms that confer therapy-induced drug resistance have been extensively investigated to explore how to com...Dear Editor,Multidrug resistance(MDR)is still a major challenge for successful cancer treatments.Numerous mechanisms that confer therapy-induced drug resistance have been extensively investigated to explore how to combat the MDR.In this regard,lysosomal sequestration has demonstrated to be a mechanism contributing to drug resistance via an/,off-target,/effect in which hydrophobic and weakly basic chemotherapeutic agents are trapped in lysosomes,sequestering them from their targets.展开更多
基金supported by the National Natural Science Foundation of China(81473238,81872896,and 81874293)the Shandong Key Innovative Research Program(2018CXGC1216,China)
文摘It is critical to regulate the senescence-associated secretory phenotype(SASP) due to its effect on promoting malignant phenotypes and limiting the efficiency of cancer therapy. In this study, we demonstrated that marchantin M(Mar-M, a naturally occurring bisbibenzyl) suppressed proinflammatory SASP components which were elevated in chemotherapy-resistant cells. Mar-M treatment attenuated the pro-tumorigenic effects of SASP and enhanced survival in drug-resistant mouse models.No toxicity was detected on normal fibroblast cells or in animals following this treatment. Inactivation of transcription factor EB(TFEB) and nuclear factor-k B(NF-k B) by Mar-M significantly accounted for its suppression on the components of SASP. Furthermore, inhibition of SASP by Mar-M contributed to a synergistic effect during co-treatment with doxorubicin to lower toxicity and enhance antitumor efficacy. Thus, chemotherapy-driven pro-inflammatory activity, seen to contribute to drug-resistance, is an important target for Mar-M. By decreasing SASP, Mar-M may be a potential approach to overcome tumor malignancy.
文摘Dear Editor,Multidrug resistance(MDR)is still a major challenge for successful cancer treatments.Numerous mechanisms that confer therapy-induced drug resistance have been extensively investigated to explore how to combat the MDR.In this regard,lysosomal sequestration has demonstrated to be a mechanism contributing to drug resistance via an/,off-target,/effect in which hydrophobic and weakly basic chemotherapeutic agents are trapped in lysosomes,sequestering them from their targets.
