Breast cancer resistance protein(BCRP)/ATP-binding cassette subfamily G member 2(ABCG2) is an ATP-binding cassette(ABC) transporter identified as a molecular cause of multidrug resistance(MDR) in diverse cancer cells....Breast cancer resistance protein(BCRP)/ATP-binding cassette subfamily G member 2(ABCG2) is an ATP-binding cassette(ABC) transporter identified as a molecular cause of multidrug resistance(MDR) in diverse cancer cells.BCRP physiologically functions as a part of a self-defense mechanism for the organism;it enhances elimination of toxic xenobiotic substances and harmful agents in the gut and biliary tract,as well as through the blood-brain,placental,and possibly blood-testis barriers.BCRP recognizes and transports numerous anticancer drugs including conventional chemotherapeutic and targeted small therapeutic molecules relatively new in clinical use.Thus,BCRP expression in cancer cells directly causes MDR by active efflux of anticancer drugs.Because BCRP is also known to be a stem cell marker,its expression in cancer cells could be a manifestation of metabolic and signaling pathways that confer multiple mechanisms of drug resistance,self-renewal(stemness),and invasiveness(aggressiveness),and thereby impart a poor prognosis.Therefore,blocking BCRP-mediated active efflux may provide a therapeutic benefit for cancers.Delineating the precise molecular mechanisms for BCRP gene expression may lead to identification of a novel molecular target to modulate BCRP-mediated MDR.Current evidence suggests that BCRP gene transcription is regulated by a number of trans-acting elements including hypoxia inducible factor 1α,estrogen receptor,and peroxisome proliferator-activated receptor.Furthermore,alternative promoter usage,demethylation of the BCRP promoter,and histone modification are likely associated with drug-induced BCRP overexpression in cancer cells.Finally,PI3K/AKT signaling may play a critical role in modulating BCRP function under a variety of conditions.These biological events seem involved in a complicated manner.Untangling the events would be an essential first step to developing a method to modulate BCRP function to aid patients with cancer.This review will present a synopsis of the impact of BCRP-mediated MDR in cancer cells,and the molecular mechanisms of acquired MDR currently postulated in a variety of human cancers.展开更多
Relapse and metastasis are frequent in colon cancer and may be linked to stem cell characteristics.This study isolated side population（SP） cells from a colon cancer cell line（Colo-320） and examined their self-rene...Relapse and metastasis are frequent in colon cancer and may be linked to stem cell characteristics.This study isolated side population（SP） cells from a colon cancer cell line（Colo-320） and examined their self-renewal and differentiation abilities.Compared to non-SP（NSP） cells,SP colon cancer cells were more tumorigenic in vivo and exhibited more invasive characteristics and a greater ability to form colonies.Additionally,more cells were in G0/G1 phase and more highly expressed the multidrug resistance protein BCRP/ABCG2.We achieved enhanced chemotherapy sensitivity by transfecting SP cells with a hairpin-like,small interfering RNA（si RNA） eukaryotic expression plasmid targeting BCRP/ABCG2.展开更多
目的观察ABCG2在肺癌和癌周肺组织的表达,从量化角度阐明其在肺癌组织中表达的病理学意义。方法常规石蜡包埋、HE切片确诊,用免疫组化SP法检测ABCG2在肺癌和癌周肺组织的定位和表达,用LeicaQ500MC图像分析系统对其表达强度进行定量分析...目的观察ABCG2在肺癌和癌周肺组织的表达,从量化角度阐明其在肺癌组织中表达的病理学意义。方法常规石蜡包埋、HE切片确诊,用免疫组化SP法检测ABCG2在肺癌和癌周肺组织的定位和表达,用LeicaQ500MC图像分析系统对其表达强度进行定量分析,并用表达的阳性单位(positive unit PU)反映其表达强度。结果ABCG2蛋白在肺癌和癌周正常肺组织中的表达主要定位在细胞质和细胞膜。在癌周正常肺组织的支气管和细支气管上皮呈弥漫表达,腺上皮呈灶性表达;肺鳞癌和肺腺癌弥漫或大片表达,肺鳞癌表达的PU值高于肺腺癌(P<0.001),肺大细胞癌和肺小细胞癌不表达,PU值接近于零。癌周肺组织表达的PU值高于各型肺癌(P<0.05)。AB-CG2蛋白表达的PU值在肺癌原发灶和转移灶之间无差别(P>0.05),且与肺癌患者的性别、年龄、转移和TNM分期未见明显相关性(P>0.05),与肺癌分化程度有关(P<0.001)。分化程度越高,PU值越高,但高分化肺癌和癌周肺组织的表达PU值差异无显著性(P>0.05)。结论ABCG2蛋白表达程度与肺癌类型及分化程度具有相关性,可能成为判断其指标之一。展开更多
目的:探讨干细胞标志物ABCG2作为肺癌干细胞标志的意义。方法:常规石蜡包埋、切片及HE染色,应用免疫组化SP法检测ABCG2在肺癌组织及肺癌细胞系GLC-82和A549中的定位和表达。显微镜观察ABCG2蛋白表达的部位及分布,用Lei-caQ500MC图像分...目的:探讨干细胞标志物ABCG2作为肺癌干细胞标志的意义。方法:常规石蜡包埋、切片及HE染色,应用免疫组化SP法检测ABCG2在肺癌组织及肺癌细胞系GLC-82和A549中的定位和表达。显微镜观察ABCG2蛋白表达的部位及分布,用Lei-caQ500MC图像分析系统对其表达强度的阳性单位(positive unit PU)进行定量测试分析。结果:ABCG2蛋白表达在肺癌细胞的胞质和胞膜;肺癌组织中肺鳞癌和肺腺癌呈阳性表达,弥漫分布;肺大细胞癌和肺小细胞癌不表达。ABCG2蛋白表达阳性率和表达强度在肺腺癌中表达最高,其次为肺鳞癌,肺小细胞癌及肺大细胞癌表达最低(P<0.05),且两者之间表达差异无显著性(P>0.05)。ABCG2蛋白在肺癌淋巴结转移灶中的表达特点与原发灶一致,但转移灶中腺癌和鳞癌表达阳性率的差异无显著性(χ2=0.36,P>0.05)。ABCG2蛋白在肺癌细胞系GLC-82和A549中呈弥漫阳性表达。结论:ABCG2单独不适合作为肺癌干细胞的标志物,但可作为肺癌分型的标记物。展开更多
Metabolic Dysfunction-Associated Steatotic Liver Disease(MASLD)has emerged as a predominant cause of chronic liver disease globally,with its prevalence rising steadily each year.If left untreated,MASLD may progress to...Metabolic Dysfunction-Associated Steatotic Liver Disease(MASLD)has emerged as a predominant cause of chronic liver disease globally,with its prevalence rising steadily each year.If left untreated,MASLD may progress to metabolic dysfunction in associated steatohepatitis(MASH),a more severe condition that can irreversibly advance to liver fibrosis,cirrhosis,and even hepatocyte carcinoma(HCC).Recent studies have illuminated a pivotal link between dysregulated cholesterol metabolism and the pathogenesis and severity of MASLD.This underscores the critical need for a comprehensive exploration of the regulatory mechanisms underlying hepatic cholesterol metabolism in MASLD,as such insights could unveil new therapeutic targets and pave the way for early diagnosis and effective prevention strategies.Cyclocarya paliurus(Batal.)Iljinskaja,a plant known for both medicinal and dietary applications,has demonstrated diverse pharmacological properties,including hypoglycemic,lipid-regulating,and hepatoprotective effects.This study aimed to investigate the hypolipidemic and hepatoprotective activities of Cyclocarya paliurus extract(CCE)in a murine model of MASLD induced by a methionine-choline-deficient(MCD)diet.Simvastatin was employed as a positive control drug,while various doses of CCE were administered to assess its therapeutic potential.Meanwhile,the control and model groups received 0.5%sodium carboxymethyl cellulose(CMC-Na)once daily for 6 weeks.At the end of the treatment period,blood and liver samples were collected for biochemical analysis,histopathological assessment,and gene expression profiling.The findings revealed that CCE significantly reduced serum levels of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)while enhancing the activities of cholinesterase(CHE)and high-density lipoprotein cholesterol(HDL-C).In liver tissues,CCE markedly decreased the levels of total cholesterol(TC)and triglycerides(TG),while simultaneously increasing hepatic HDL-C content.Histological analyses showed notable alleviation of pathological liver damage in CCE-treated mice.Molecular studies further demonstrated that CCE downregulated the expression of key genes and proteins involved in cholesterol synthesis,including SREBP2,LDLR,and HMGCR.Concurrently,it upregulated the expression of genes and proteins related to cholesterol transport,such as ABCG5 and ABCG8.Additionally,CCE mitigated inflammation by improving the expression levels of pro-inflammatory cytokines,including TNF-α and IL-6,and modulated oxidative stress markers,such as NRF2,KEAP1,and NQO1.Protein expression analyses revealed reduced levels of IL-6 and IL-1β,further corroborating its anti-inflammatory effects.In summary,C.paliurus exhibited potent hepatoprotective effects in MCD-induced MASLD mice.These protective mechanisms were closely linked to the upregulation of cholesterol transporters ABCG5/8 and the modulation of sterol regulatory element-binding protein 2(SREBP2).This study highlighted the therapeutic potential of C.paliurus as a promising intervention for MASLD and underscored its role in regulating cholesterol metabolism and mitigating inflammation and oxidative stress.展开更多
背景与目的:三磷酸腺苷结合盒转运体成员ABCG2(ATP-binding cassette superfamily G member2)是源于造血干细胞的标志物之一,其在神经胶质瘤发生发展相关组织和细胞中的表达情况还不清楚。本研究检测ABCG2在不同恶性程度人脑胶质瘤组织...背景与目的:三磷酸腺苷结合盒转运体成员ABCG2(ATP-binding cassette superfamily G member2)是源于造血干细胞的标志物之一,其在神经胶质瘤发生发展相关组织和细胞中的表达情况还不清楚。本研究检测ABCG2在不同恶性程度人脑胶质瘤组织标本、裸小鼠移植瘤标本、体外细胞系球体和胶质瘤干细胞球体中的表达情况并分析其意义。方法:制作布有不同恶性程度人脑胶质瘤组织标本、裸小鼠移植瘤标本、体外细胞系球体和胶质瘤干细胞球体等的组织芯片,用免疫组化方法检测ABCG2在组织芯片中的表达情况。结果:在71例人脑胶质瘤组织标本中ABCG2的阳性率为26.8%,其中Ⅰ级11.1%,Ⅱ级8.0%,Ⅲ级43.5%,Ⅳ级42.9%;Ⅰ～Ⅱ级与Ⅲ～Ⅳ级相比差异具有统计学意义(%2=10.710,P=0.001)。在神经干细胞、裸小鼠移植瘤、胶质瘤干细胞球体表达率为100%。在多种正常组织中亦有不同程度的表达。在胶质瘤临床标本中ABCG2阳性细胞呈亲血管分布。结论:ABCG2在胶质瘤干细胞、恶性程度高的胶质瘤组织标本和移植瘤组织中高表达,并且呈亲血管分布。展开更多
文摘Breast cancer resistance protein(BCRP)/ATP-binding cassette subfamily G member 2(ABCG2) is an ATP-binding cassette(ABC) transporter identified as a molecular cause of multidrug resistance(MDR) in diverse cancer cells.BCRP physiologically functions as a part of a self-defense mechanism for the organism;it enhances elimination of toxic xenobiotic substances and harmful agents in the gut and biliary tract,as well as through the blood-brain,placental,and possibly blood-testis barriers.BCRP recognizes and transports numerous anticancer drugs including conventional chemotherapeutic and targeted small therapeutic molecules relatively new in clinical use.Thus,BCRP expression in cancer cells directly causes MDR by active efflux of anticancer drugs.Because BCRP is also known to be a stem cell marker,its expression in cancer cells could be a manifestation of metabolic and signaling pathways that confer multiple mechanisms of drug resistance,self-renewal(stemness),and invasiveness(aggressiveness),and thereby impart a poor prognosis.Therefore,blocking BCRP-mediated active efflux may provide a therapeutic benefit for cancers.Delineating the precise molecular mechanisms for BCRP gene expression may lead to identification of a novel molecular target to modulate BCRP-mediated MDR.Current evidence suggests that BCRP gene transcription is regulated by a number of trans-acting elements including hypoxia inducible factor 1α,estrogen receptor,and peroxisome proliferator-activated receptor.Furthermore,alternative promoter usage,demethylation of the BCRP promoter,and histone modification are likely associated with drug-induced BCRP overexpression in cancer cells.Finally,PI3K/AKT signaling may play a critical role in modulating BCRP function under a variety of conditions.These biological events seem involved in a complicated manner.Untangling the events would be an essential first step to developing a method to modulate BCRP function to aid patients with cancer.This review will present a synopsis of the impact of BCRP-mediated MDR in cancer cells,and the molecular mechanisms of acquired MDR currently postulated in a variety of human cancers.
基金supported by grants from the National Nature Science Foundation of China(No.81101870)the National Key Clinical Specialist Construction Programs of China(No.2013-544)the Key Programs of National Health and Family Planning Commission of Tianjin(No.16KG127)
文摘Relapse and metastasis are frequent in colon cancer and may be linked to stem cell characteristics.This study isolated side population（SP） cells from a colon cancer cell line（Colo-320） and examined their self-renewal and differentiation abilities.Compared to non-SP（NSP） cells,SP colon cancer cells were more tumorigenic in vivo and exhibited more invasive characteristics and a greater ability to form colonies.Additionally,more cells were in G0/G1 phase and more highly expressed the multidrug resistance protein BCRP/ABCG2.We achieved enhanced chemotherapy sensitivity by transfecting SP cells with a hairpin-like,small interfering RNA（si RNA） eukaryotic expression plasmid targeting BCRP/ABCG2.
文摘目的观察ABCG2在肺癌和癌周肺组织的表达,从量化角度阐明其在肺癌组织中表达的病理学意义。方法常规石蜡包埋、HE切片确诊,用免疫组化SP法检测ABCG2在肺癌和癌周肺组织的定位和表达,用LeicaQ500MC图像分析系统对其表达强度进行定量分析,并用表达的阳性单位(positive unit PU)反映其表达强度。结果ABCG2蛋白在肺癌和癌周正常肺组织中的表达主要定位在细胞质和细胞膜。在癌周正常肺组织的支气管和细支气管上皮呈弥漫表达,腺上皮呈灶性表达;肺鳞癌和肺腺癌弥漫或大片表达,肺鳞癌表达的PU值高于肺腺癌(P<0.001),肺大细胞癌和肺小细胞癌不表达,PU值接近于零。癌周肺组织表达的PU值高于各型肺癌(P<0.05)。AB-CG2蛋白表达的PU值在肺癌原发灶和转移灶之间无差别(P>0.05),且与肺癌患者的性别、年龄、转移和TNM分期未见明显相关性(P>0.05),与肺癌分化程度有关(P<0.001)。分化程度越高,PU值越高,但高分化肺癌和癌周肺组织的表达PU值差异无显著性(P>0.05)。结论ABCG2蛋白表达程度与肺癌类型及分化程度具有相关性,可能成为判断其指标之一。
文摘目的:探讨干细胞标志物ABCG2作为肺癌干细胞标志的意义。方法:常规石蜡包埋、切片及HE染色,应用免疫组化SP法检测ABCG2在肺癌组织及肺癌细胞系GLC-82和A549中的定位和表达。显微镜观察ABCG2蛋白表达的部位及分布,用Lei-caQ500MC图像分析系统对其表达强度的阳性单位(positive unit PU)进行定量测试分析。结果:ABCG2蛋白表达在肺癌细胞的胞质和胞膜;肺癌组织中肺鳞癌和肺腺癌呈阳性表达,弥漫分布;肺大细胞癌和肺小细胞癌不表达。ABCG2蛋白表达阳性率和表达强度在肺腺癌中表达最高,其次为肺鳞癌,肺小细胞癌及肺大细胞癌表达最低(P<0.05),且两者之间表达差异无显著性(P>0.05)。ABCG2蛋白在肺癌淋巴结转移灶中的表达特点与原发灶一致,但转移灶中腺癌和鳞癌表达阳性率的差异无显著性(χ2=0.36,P>0.05)。ABCG2蛋白在肺癌细胞系GLC-82和A549中呈弥漫阳性表达。结论:ABCG2单独不适合作为肺癌干细胞的标志物,但可作为肺癌分型的标记物。
基金National Key Research and Development Program of China(Grant No.2022YFC3501700)the Beijing Municipal Natural Science Foundation(Grant No.7144219).
文摘Metabolic Dysfunction-Associated Steatotic Liver Disease(MASLD)has emerged as a predominant cause of chronic liver disease globally,with its prevalence rising steadily each year.If left untreated,MASLD may progress to metabolic dysfunction in associated steatohepatitis(MASH),a more severe condition that can irreversibly advance to liver fibrosis,cirrhosis,and even hepatocyte carcinoma(HCC).Recent studies have illuminated a pivotal link between dysregulated cholesterol metabolism and the pathogenesis and severity of MASLD.This underscores the critical need for a comprehensive exploration of the regulatory mechanisms underlying hepatic cholesterol metabolism in MASLD,as such insights could unveil new therapeutic targets and pave the way for early diagnosis and effective prevention strategies.Cyclocarya paliurus(Batal.)Iljinskaja,a plant known for both medicinal and dietary applications,has demonstrated diverse pharmacological properties,including hypoglycemic,lipid-regulating,and hepatoprotective effects.This study aimed to investigate the hypolipidemic and hepatoprotective activities of Cyclocarya paliurus extract(CCE)in a murine model of MASLD induced by a methionine-choline-deficient(MCD)diet.Simvastatin was employed as a positive control drug,while various doses of CCE were administered to assess its therapeutic potential.Meanwhile,the control and model groups received 0.5%sodium carboxymethyl cellulose(CMC-Na)once daily for 6 weeks.At the end of the treatment period,blood and liver samples were collected for biochemical analysis,histopathological assessment,and gene expression profiling.The findings revealed that CCE significantly reduced serum levels of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)while enhancing the activities of cholinesterase(CHE)and high-density lipoprotein cholesterol(HDL-C).In liver tissues,CCE markedly decreased the levels of total cholesterol(TC)and triglycerides(TG),while simultaneously increasing hepatic HDL-C content.Histological analyses showed notable alleviation of pathological liver damage in CCE-treated mice.Molecular studies further demonstrated that CCE downregulated the expression of key genes and proteins involved in cholesterol synthesis,including SREBP2,LDLR,and HMGCR.Concurrently,it upregulated the expression of genes and proteins related to cholesterol transport,such as ABCG5 and ABCG8.Additionally,CCE mitigated inflammation by improving the expression levels of pro-inflammatory cytokines,including TNF-α and IL-6,and modulated oxidative stress markers,such as NRF2,KEAP1,and NQO1.Protein expression analyses revealed reduced levels of IL-6 and IL-1β,further corroborating its anti-inflammatory effects.In summary,C.paliurus exhibited potent hepatoprotective effects in MCD-induced MASLD mice.These protective mechanisms were closely linked to the upregulation of cholesterol transporters ABCG5/8 and the modulation of sterol regulatory element-binding protein 2(SREBP2).This study highlighted the therapeutic potential of C.paliurus as a promising intervention for MASLD and underscored its role in regulating cholesterol metabolism and mitigating inflammation and oxidative stress.
文摘背景与目的:三磷酸腺苷结合盒转运体成员ABCG2(ATP-binding cassette superfamily G member2)是源于造血干细胞的标志物之一,其在神经胶质瘤发生发展相关组织和细胞中的表达情况还不清楚。本研究检测ABCG2在不同恶性程度人脑胶质瘤组织标本、裸小鼠移植瘤标本、体外细胞系球体和胶质瘤干细胞球体中的表达情况并分析其意义。方法:制作布有不同恶性程度人脑胶质瘤组织标本、裸小鼠移植瘤标本、体外细胞系球体和胶质瘤干细胞球体等的组织芯片,用免疫组化方法检测ABCG2在组织芯片中的表达情况。结果:在71例人脑胶质瘤组织标本中ABCG2的阳性率为26.8%,其中Ⅰ级11.1%,Ⅱ级8.0%,Ⅲ级43.5%,Ⅳ级42.9%;Ⅰ～Ⅱ级与Ⅲ～Ⅳ级相比差异具有统计学意义(%2=10.710,P=0.001)。在神经干细胞、裸小鼠移植瘤、胶质瘤干细胞球体表达率为100%。在多种正常组织中亦有不同程度的表达。在胶质瘤临床标本中ABCG2阳性细胞呈亲血管分布。结论:ABCG2在胶质瘤干细胞、恶性程度高的胶质瘤组织标本和移植瘤组织中高表达,并且呈亲血管分布。
