RESUMEN
OBJECTIVE: To study the effect and mechanism of Huayu Wan (, HYW) in combination of chemotherapy of tumor treatment. METHODS: HYW serum was added in Lewis cells to assess its impact on fluorescent doxorubicin delivery in vitro. Then, Lewis tumor cells was implanted in C57BL/6 mice via xenograft transplantation. Tumor growth was measured and signal intensity corresponding to blood flow was assessed by laser doppler perfusion imaging (LDPI). Finally, the effect of HYW on the effificacy of doxorubicin was studied. RESULTS: HYW can improve the transfer of fluorescent doxorubicin into cells. The blood flow signal in the tumor tissues of the HYW group was higher than that of the control group (P<0.01). Furthermore, HYW improved drug delivery of doxorubicin to tumor tissues, and this activity was associated with HYW-induced microvascular proliferation (P<0.01). CONCLUSIONS: HYW can promote microangiogenesis and increase blood supply in tumor tissues, which in turn may increase the risk of metastasis. At the same time, HYW increases drug delivery and improves the effificacy of chemotherapy drugs through vascular proliferation. Therefore, rational judgment must be exercised when considering applying HYW to an antitumor regimen.
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Doxorrubicina , Neoplasias Pulmonares , Animales , Línea Celular Tumoral , Doxorrubicina/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Ratones , Ratones Endogámicos C57BL , Ratones Desnudos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Colon cancer arises from the accumulations of genetic and epigenetic changes. Currently, profiles of DNA methylation and gene expression of colon cancer have not been elucidated clearly. This articles aims to characterize the profile of DNA methylation and gene expression of colon cancer systemically, and acquire candidate genes potentially regulated by altered methylation for this disease.Data were downloaded from The Cancer Genome Atlas database. Differentially methylated CpG sites (DMCs) and differentially methylated regions (DMRs) were calculated via COHCAP. Differentially expressed genes (DEGs) were identified by DESeq2. Weighted gene co-expression network analysis (WGCNA) package in R was applied for WGCNA.Data of 275 solid tumor tissues and 19 adjacent tumor tissues of colon cancer were obtained. A total of 1828 DMCs, including 1390 hypermethylated and 438 hypomethylated CpG sites, were identified between tumor and normal groups. A total of 789 DEGs, containing 435 upregulated genes and 354 downregulated genes were observed. It revealed that 8 DMRs-DEGs and 95 DMCs-DEGs pairs were significantly correlated. Furthermore, genes of yellow and brown modules from WGCNA were significantly correlated with tumor/normal status, and significantly enriched in peroxisome proliferator activated receptor signaling pathway, glutamatergic synapse, and neuroactive ligand-receptor interaction. Genes in the above 2 modules were also significantly enriched in DMCs or DMRs-associated genes. Specifically, ADHFE1, HAND2, and GNAO1 were hypermethylated and downregulated in colon cancer, suggesting that the low expression levels of these genes may be regulated by DNA hypermethylation. In addition, the 3 genes were involved in brown module of WGCNA, indicating their important roles in colon cancer.The investigation of the relationship between DNA methylation and gene expression may help to understand the effect of DNA methylation alteration on genes expression, especially gene co-expression network in the development of colon cancer. Genes such as ADHFE1, HAND2, and GNAO1 may be served as potential candidates for diagnosis and therapy targets in colon cancer.
Asunto(s)
Neoplasias del Colon/genética , Neoplasias del Colon/fisiopatología , Metilación de ADN/fisiología , Expresión Génica/fisiología , Oxidorreductasas de Alcohol/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Islas de CpG/fisiología , Bases de Datos Genéticas , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/metabolismo , Redes Reguladoras de Genes/fisiología , Humanos , Proteínas Mitocondriales/metabolismo , Receptores Activados del Proliferador del Peroxisoma/metabolismo , Transducción de Señal/fisiologíaRESUMEN
OBJECTIVE: To explore the effect of Lignum Sappan (LS) containing serum on the proliferation cycle arrest of human lung cancer cell line PG and its molecular mechanism. METHODS: The lung cancer PG cells were divided into four groups, i.e., the blank control group, the LS group, the LS plus cisplatin group, and the cisplatin group. They were cultured by RPMI-1640 with 20% blank serum, RPMI-1640 with 20% LS containing serum, RPMI-1640 with 20% LS containing serum plus 1 microg/mL cisplatin, and RPMI-1640 with 20% blank serum plus 1 microg/mL cisplatin, respectively. The morphology of PG cells was observed using light microscope and laser scanning confocal microscope in each group. The cell cycle arrest was observed using flow cytometry. The expression of P16 and Rb1 mRNA was tested by PCR method. RESULTS: Under the light microscope and laser scanning confocal microscope, the apoptosis degree of PG cells in the LS group was significant, but less than that of the LS plus cisplatin group as well as the cisplatin group. Compared with the blank control group, the proportion of PG cells increased at G0/ G1 and S phases (P < 0.05) and decreased at G2/M phase (P < 0.01) in the LS group; The proportion of PG cells increased at G2/M and S phases (P < 0.05, P < 0.01) and decreased at G0/G1 phase (P < 0.01) in the LS plus cisplatin group as well as the cisplatin group. Compared with the LS group, the proportion of PG cells increased at G2/M and S phases (P < 0.05, P < 0.01) and decreased at G0/G1 phase (P < 0.01) in the LS plus cisplatin group as well as the cisplatin group. There was no statistical difference in PG cells at each phase between the cisplatin group and the LS plus cisplatin group (P > 0.05). The expression of P16 and Rb1 mRNA increased in the LS group, when compared with the blank control group. They also increased in the cisplatin group and the LS plus cisplatin group, higher than that of the LS group (P < 0.05). There was no statistical difference in the expression of P16 and Rb1 mRNA between the cisplatin group and the LS plus cisplatin group (P > 0.05). CONCLUSION: LS containing serum induced PG cell apoptosis by up-regulating the mRNA transcription levels of P16 and Rb1, thus resulting in PG cell arrest at G0/G1 and S phases, which was different from the manner of cisplatin (achieved by arresting PG cells at G2/M and S phases through regulating cyclinB1 mRNA transcription).