Colorectal cancer(CRC)ranks third in the number of cancers mainly because of the inability to diagnose it at an early stage.The pathogenesis of CRC is complicated,which is the result of the complex interaction of mult...Colorectal cancer(CRC)ranks third in the number of cancers mainly because of the inability to diagnose it at an early stage.The pathogenesis of CRC is complicated,which is the result of the complex interaction of multiple genetic and environmental factors.Currently,one of the main treatments for CRC is chemotherapy.But the primary cause of CRC treatment failure is drug resistance.The expression of cyclin-dependent kinase 9(CDK9)was correlated with elevated autophagy levels in colon cancer,and high expression of CDK9 indicates a poor prognosis in CRC.The incidence of autophagy and the expressions of Beclin 1 and ATP binding cassette transporter G2 are different in left and right colon cancer,and autophagy may be involved in the occurrence of chemotherapy resistance.In this article,the roles of CDK9,ATP binding cassette transporter G2 and Beclin 1 in CRC were elucidated,emphasizing the linkages among them and providing potential therapeutic targets of CRC.展开更多
Atherosclerosis is the most common cause of cardiovascular diseases, such as myocardial infarction and stroke. The aim of this study was to investigate the effects of a novel compound ZBM30 on atherosclerosis in ApoE-...Atherosclerosis is the most common cause of cardiovascular diseases, such as myocardial infarction and stroke. The aim of this study was to investigate the effects of a novel compound ZBM30 on atherosclerosis in ApoE- deficient mice and its associated mechanism. ApoE-deficient mice （6 weeks old）, fed an atherogenic high-fat and high cholesterol diet for 8 weeks, were divided into three groups. Two groups were orally administrated ZBM30 （10, 30 nag ~ kg-1） daily for 12 weeks, while the control group was administered saline. Atherosclerotic lesions with en face aortas were evaluated by Sudan IV staining, and lesion areas in aortic sinuses were evaluated by oil red O staining. Necrotic core areas and fibrous cap areas in the lesion were evaluated by henaatoxylin and eosin （HE） staining and Masson＇ s trichronae staining in the aorta sinuses. The effects of ZBM30 on cholesterol accumulation in naacrophages and cholesterol transporters： ATP binding cassette A1 （ABCA1） and ATP binding cassette G1 （AB- CG1） were evaluated by oil red O assay, 3H-cholesterol efflux assay, Western blot, and real-time PCR on macro- phage cell lines： Raw 264.7 and THP-1. Inanauno-fluoresces was used to determine the ABCA1 expression in naac- rophage in aorta sinuses. Luciferase reporters of wild type and mutant types of ABCA1 promoter were constructed to determine the regulatory domain of ZBM30 on ABCA1 promoter. Results showed that, compared with the control group, en face lesions in ZBM30 group （ 10, 30 mg · kg^-1 ） were reduced 54.96 ± 10.06% and 71.50 ± 15.37% respectively, and aorta sinus lesions were reduced 41.85 ± 11.21% and 82.23 ± 8.25% respectively. Necrotic core areas in the ZBM30 group were markedly reduced and fibrous cap areas were not changed. Oil red O staining and 3 H-cholesterol efflux assays on Raw 264.7 cell line revealed that ZBM30 significantly attenuated the cholesterol accumulation in naacrophages by enhancing apolipoprotein AI and HDL mediated cholesterol efflux. Furthermore, ZBM30 induced the protein and naRNA expression of cholesterol transporters such as ABCA1 and ABCG1. Inanauno- fluoresces experiment revealed that ZBM30 induced the ABCA1 expression in naacrophage in the lesion, which is consistent with the results in vitro. Luciferase reporter assay revealed that ZBM30 exerted its effect on ABCA1 via liver X receptor （LXR） binding domain. In conclusion, ZBM30 suppresses atherosclerosis through up-regulating cholesterol efflux via ABCA1 and ABCG1 transporters in ApoE-deficient mice.展开更多
基金Supported by the National Natural Science Foundation of China,No.82272996the Science and Technology Program of Guangzhou,No.202206010081.
文摘Colorectal cancer(CRC)ranks third in the number of cancers mainly because of the inability to diagnose it at an early stage.The pathogenesis of CRC is complicated,which is the result of the complex interaction of multiple genetic and environmental factors.Currently,one of the main treatments for CRC is chemotherapy.But the primary cause of CRC treatment failure is drug resistance.The expression of cyclin-dependent kinase 9(CDK9)was correlated with elevated autophagy levels in colon cancer,and high expression of CDK9 indicates a poor prognosis in CRC.The incidence of autophagy and the expressions of Beclin 1 and ATP binding cassette transporter G2 are different in left and right colon cancer,and autophagy may be involved in the occurrence of chemotherapy resistance.In this article,the roles of CDK9,ATP binding cassette transporter G2 and Beclin 1 in CRC were elucidated,emphasizing the linkages among them and providing potential therapeutic targets of CRC.
文摘Atherosclerosis is the most common cause of cardiovascular diseases, such as myocardial infarction and stroke. The aim of this study was to investigate the effects of a novel compound ZBM30 on atherosclerosis in ApoE- deficient mice and its associated mechanism. ApoE-deficient mice （6 weeks old）, fed an atherogenic high-fat and high cholesterol diet for 8 weeks, were divided into three groups. Two groups were orally administrated ZBM30 （10, 30 nag ~ kg-1） daily for 12 weeks, while the control group was administered saline. Atherosclerotic lesions with en face aortas were evaluated by Sudan IV staining, and lesion areas in aortic sinuses were evaluated by oil red O staining. Necrotic core areas and fibrous cap areas in the lesion were evaluated by henaatoxylin and eosin （HE） staining and Masson＇ s trichronae staining in the aorta sinuses. The effects of ZBM30 on cholesterol accumulation in naacrophages and cholesterol transporters： ATP binding cassette A1 （ABCA1） and ATP binding cassette G1 （AB- CG1） were evaluated by oil red O assay, 3H-cholesterol efflux assay, Western blot, and real-time PCR on macro- phage cell lines： Raw 264.7 and THP-1. Inanauno-fluoresces was used to determine the ABCA1 expression in naac- rophage in aorta sinuses. Luciferase reporters of wild type and mutant types of ABCA1 promoter were constructed to determine the regulatory domain of ZBM30 on ABCA1 promoter. Results showed that, compared with the control group, en face lesions in ZBM30 group （ 10, 30 mg · kg^-1 ） were reduced 54.96 ± 10.06% and 71.50 ± 15.37% respectively, and aorta sinus lesions were reduced 41.85 ± 11.21% and 82.23 ± 8.25% respectively. Necrotic core areas in the ZBM30 group were markedly reduced and fibrous cap areas were not changed. Oil red O staining and 3 H-cholesterol efflux assays on Raw 264.7 cell line revealed that ZBM30 significantly attenuated the cholesterol accumulation in naacrophages by enhancing apolipoprotein AI and HDL mediated cholesterol efflux. Furthermore, ZBM30 induced the protein and naRNA expression of cholesterol transporters such as ABCA1 and ABCG1. Inanauno- fluoresces experiment revealed that ZBM30 induced the ABCA1 expression in naacrophage in the lesion, which is consistent with the results in vitro. Luciferase reporter assay revealed that ZBM30 exerted its effect on ABCA1 via liver X receptor （LXR） binding domain. In conclusion, ZBM30 suppresses atherosclerosis through up-regulating cholesterol efflux via ABCA1 and ABCG1 transporters in ApoE-deficient mice.
文摘目的:探讨不同分子靶向药物对高表达与低表达ATP结合转运蛋白G超家族成员2(ATP-binding cassette super-family Gmember 2,ABCG2)的人耐药鼻咽癌CNE2/DDP细胞(分别简写为ABCG2highCNE2/DDP和ABCG2lowCNE2/DDP)表面NKG2D配体(natural killer group 2 member Dligands,NKG2DLs)表达的诱导作用及其对NK细胞杀伤敏感性的影响。方法:免疫磁珠法分选ABCG2highCNE2/DDP、ABCG2lowCNE2/DDP细胞及NK细胞。流式细胞术检测分选细胞的纯度和不同分子靶向药物(硼替佐米、索拉非尼、舒尼替尼)处理前后ABCG2highCNE2/DDP和ABCG2lowCNE2/DDP细胞NKG2DLs的表达率。LDH释放法检测不同药物处理前后ABCG2highCNE2/DDP和ABCG2lowCNE2/DDP细胞对NK细胞杀伤的敏感性。结果:ABCG2highCNE2/DDP和ABCG2lowCNE2/DDP细胞表面ABCG2的表达率分别为(91.40±2.32)%和(1.70±0.24)%。分选后NK细胞中CD3-CD16+CD56+细胞的比例达90%以上。药物处理前,ABCG2highCNE2/DDP和ABCG2lowCNE2/DDP细胞MICA、MICB、ULBP1、ULBP2和ULBP3呈弱表达;经不同分子靶向药物处理后,5种NKG2DLs的表达率均明显上升(P<0.01),以舒尼替尼处理后NKG2DLs的表达率升高最明显。随着NKG2DLs表达的上调,ABCG2highCNE2/DDP和ABCG2lowCNE2/DDP细胞对NK细胞杀伤的敏感性也随之升高。结论:不同分子靶向药物可诱导耐药鼻咽癌CNE2/DDP细胞NKG2DLs的表达,以舒尼替尼的诱导作用最强,且肿瘤细胞NKG2DLs的表达与其对NK细胞杀伤敏感性之间存在线性关系。
