关键词： ALT, glutamic-pyruvic transaminase AST, transaminase BUN, blood urea nitrogen CDDP, cisplatin CI, combinatory index CM, conditioned media CREA, creatinine CT-like, both chymotrypsin-like DMSO, dimethyl sulfoxide Doc, docetaxel Doxo, doxorubicin Drug resistance EdU, 5-ethynyl-2′-deoxyuridine LPS, lipopolysaccharide MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Mar-M, Marchantin M Marchantin M NF-κB NF-κB, nuclear factor-κB PGPH, peptidylglutamyl hydrolyzing PI, propidium iodide ROS, reactive oxygen species SA-β-gal, senescence-associated β-galactosidase SASP SASP, senescence-associated secretory phenotype Sv, starvation TCGA, the Cancer Genome Atlas TFEB TFEB, transcription factor EB Tg, thapsigargin

来  源：   DOI：10.1016/j.apsb.2019.08.007   PDF(Sci-hub)   PDF(Pubmed)

Abstract：
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 pro-inflammatory 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-κB (NF-κB) 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.
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