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Oleanolic acid inhibits colon cancer cell stemness and reverses chemoresistance by suppressing jak2/stat3 signaling pathway

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BIOCELL 2024年第7期48卷 1037-1046页

作者： RUOYU CHEN YIMAN WU FENG WANG JUNTAO ZHOU HUAZHANG ZHUANG WEI LI Department of Anus and Intestine Surgery Shenzhen Longhua District Central HospitalShenzhenChina Department of Urology Shenzhen Longhua District Central HospitalShenzhenChina

Background:Oleanolic acid(OA),a pentacyclic triterpenoid exhibiting speciﬁc anti-cancer properties and highly effective antioxidant activity,was isolated from traditional Chinese medicinal ***,the OA that impacts colon cancer(CC)cells and its underlying mechanisms remain poorly ***:The cytotoxic effect of OA alone or OA-5-Fluorouracil(5-FU)combination on normal and CC cells was analyzed by methyl thiazolyl diphenyl-tetrazolium bromide(MTT).Then,the impact of OA on CC cell lines(LoVo and HT-29)proliferation and stemness were measured using colon formation and tumorsphere formation ***-binding transcription factor 4(Oct4),Prominin-1(CD133),Nanog,and transcription factor SOX-2(SOX2)are cell stemness-related indicators whose expression was assessed usingﬂuorescence qPCR assay,Western blotting,and *** effect of OA on the proliferative potency of CC cells was evaluated using an in vivo ***:The stem-like characteristics and clone production of colon cancer cells were markedly reduced by OA alone or in combination with ***,OA increases the susceptibility of CC cells to 5-FU by blocking the cell stemness-related markers(CD133,Nanog,SOX2,and Oct4)expression levels both in vitro and in vivo,as well as by inactivating the activator of transcription 3(stat3 signaling)and Janus kinase 2/signal transducer(jak2).Conclusion:Theseﬁndings imply that oleanolic acid,both in vitro and in vivo,suppresses the jak2/stat3 pathway,which in turn reverses chemoresistance and decreases colon cancer cell ***,by reducing the recommended amount of 5-FU,this strategy may improve chemotherapeutic effectiveness and minimize undesired side effects.

关键词： Colon cancer,Oleanolic acid,Stemness,5-FU jak2/stat3 signaling pathway

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Elevated retinol binding protein 4 levels are associated with atherosclerosis in diabetic rats via jak2/stat3 signaling pathway

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World Journal of Diabetes 2021年第4期12卷 466-479页

作者： Wan Zhou Shan-Dong Ye Wei Wang Department of Endocrinology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001Anhui ProvinceChina Laboratory for Diabetes Department of EndocrinologyThe First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001Anhui ProvinceChina Institute of Endocrinology and Metabolic Diseases University of Science and Technology of ChinaHefei 230001Anhui ProvinceChina

BACKGROUND Atherosclerosis is a major cause of mortality worldwide and is driven by multiple risk factors,including diabetes,which results in an increased atherosclerotic burden,but the precise mechanisms for the occurrence and development of diabetic atheroscerosis have not been fully *** To summarize the potential role of retinol binding protein 4(RBP4) in the pathogenesis of diabetic atheroscerosis,particularly in relation to the RBP4-Janus kinase 2/signal transducer and activator of transcription 3(jak2/stat3)signaling *** Male Wistar rats were randomly divided into three groups,including a control group(NC group),diabetic rat group(DM group),and diabetic atherosclerotic rat group(DA group).The contents of total cholesterol(TC), high-density lipoprotein cholesterol(HDL-c), triglycerides(TG), low-density lipoprotein cholesterol(LDLc), fasting insulin(FINS),fasting plasma glucose,and hemoglobin A1 c(HbA1 c)were ***,the adipose and serum levels of RBP4,along with the expression levels of jak2, phosphorylated jak2(p-jak2), stat3,phosphorylated stat3(p-stat3), B-cell lymphoma-2(Bcl-2), and Cyclin D1 in aortic tissues were also ***,homeostasis model assessment of insulin resistance(HOMA-IR) and atherogenic indexes(AI) were *** Compared with the NC and DM groups,the levels LDL-c,TG,TC,FINS,HOMAIR,RBP4,and AI were upregulated,whereas that of HDL-c was downregulated in the DA group(P jak2,stat3,Cyclin D1,and Bcl-2 in the DA group were significantly increased compared with the NC group and the DM group;P-jak2,p-jak2/jak2 ratio,p-stat3,p-stat3/stat3 ratio,Cyclin D1,and Bcl-2 at protein levels were significantly upregulated in the DA group compared with the NC group and DM *** addition,as shown by Pearson analysis,serum RBP4 had a positive correlation with TG,TC,LDL-c,FINS,HbA1 C,p-jak2,p-stat3,Bcl-2,Cyclin D1,AI,and HOMA-IR but a negative correlation with *** addition,multi

关键词： Diabetes mellitus Petinol binding protein 4 Atherosclerosis jak2/stat3 signaling pathway Cyclin D1

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The spirocyclopiperazinium salt compound LXM-15 alleviates chronic inflammatory and neuropathic pain in mice and rats

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Journal of Chinese Pharmaceutical Sciences 2019年第6期28卷 371-380页

作者： Ning Li Yingying Liang Qi Sun Yimin Jiang Runtao Li Jia Ye Department of Molecular and Cellular Pharmacology School of Pharmaceutical SciencesPeking University Health ScienceCenterBeijing100191China Department of Chemical Biology School of Pharmaceutical SciencesPeking University Health Science CenterBeijing100191China Department of Medical and Healthy Analysis Center Peking University Health Science CenterBeijing100191China

In the present study,we aimed to evaluate the effect of the spirocyclopiperazinium salt compound LXM-15 on chronic inflammatory pain and chronic neuropathic pain induced by complete Freund’s adjuvant(CFA)or chronic constriction injury(CCI)in mice and *** results showed that administration with LXM-15 significantly reduced paw edema and ankle swelling and increased the mechanical withdrawal threshold and paw withdrawal latency after CFA injection in ***-15 significantly alleviated the mechanical allodynia and thermal hyperalgesia in CCI *** effect was abolished by pretreatment with hexamethonium(a peripheral nAChR antagonist)or methyllycaconitine citrate(anα7 nAChR antagonist).Furthermore,LXM-15 significantly inhibited the phosphorylation of jak2 and stat3,and suppressed the expressions of TNF-αand c-fos in dorsal root ganglia of CCI ***,we reported that LXM-15 relieved chronic inflammatory pain in CFA mice and chronic neuropathic pain in CCI *** underlying mechanism might be related to the activation of peripheralα7 nicotinic receptor,further inhibiting jak2/stat3 signaling pathway,and eventually suppressing the expressions of TNF-αand c-fos.

关键词： Spirocyclopiperazinium salt compound LXM-15 Chronic pain α7 nicotinic receptor jak2/stat3 signaling pathway

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