SCE administration resulted in observable apoptotic processes, including nuclear pyknosis, enhanced staining intensity, and nuclear fragmentation, in both susceptible and resistant cell lines, as indicated by DAPI staining. In addition, the proportion of apoptotic cells in sensitive/resistant cell lines was substantially elevated, as assessed by double staining flow cytometry, after administration of SCE. Moreover, Western blot analysis of the treated breast cancer cell lines demonstrated a significant reduction in caspase-3, caspase-9, and Bcl-2 protein levels, along with a significant increase in Bax protein expression after SCE administration. Additionally, SCE may result in an increase of positive fluorescent spots after MDC staining and yellow fluorescent spots after GFP-LC3B-mCherry transfection, and raise the expression levels of autophagy-related proteins LC3B, p62, and Beclin-1 in breast cancer cells. In conclusion, SCE might contribute to the inhibition of multidrug resistance in breast cancer cells through the blocking of cell cycle progression, the interruption of autophagic processes, and the consequential interference with the cells' resistance to apoptosis.
This research project intends to delve into the workings of Yanghe Decoction (YHD) in inhibiting subcutaneous tumors during pulmonary metastasis in breast cancer, which is anticipated to provide a foundational understanding for breast carcinoma treatment using YHD. Utilizing the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and SwissTargetPrediction, the chemical compositions and corresponding target molecules of medicinals present in YHD were retrieved. Disease targets were ascertained from the resources of GeneCards and Online Mendelian Inheritance in Man (OMIM). Screening common targets and plotting a Venn diagram were accomplished with the aid of Excel. The network illustrating protein-protein interactions was constructed. For Gene Ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, the R language was the tool of choice. To investigate the effects of YHD, 53 female SPF Bablc/6 mice were divided into four groups: a normal control group (8 mice), a model group (15 mice), and two YHD groups (15 mice each) receiving low-dose and high-dose YHD respectively. YHD was administered intraperitoneally for 30 days; all other groups received the same volume of normal saline. Each day, the procedure involved measuring body weight and the size of the tumor. The growth patterns of in situ tumors and corresponding body weight changes were graphically depicted. At the conclusion, the subcutaneous tumor sample was gathered and assessed using hematoxylin and eosin (H&E) staining. Quantitative analysis of the mRNA and protein levels of hypoxia inducible factor-1 (HIF-1), pyruvate kinase M2 (PKM2), lactate dehydrogenase A (LDHA), and glucose transporter type 1 (GLUT1) was carried out using PCR and Western blot. A screening process identified 213 active YHD components and 185 disease-related targets. The hypothesis that YHD may control glycolysis by way of the HIF-1 signaling pathway, thereby impacting breast cancer, has been formulated. In the animal experiment, the high- and low-dose YHD groups displayed lower levels of mRNA and protein for HIF-1, PKM2, LDHA, and GLUT1 in comparison with the model group's levels. Subcutaneous tumor development in pulmonary metastasis from breast cancer in the early stages is demonstrably inhibited by YHD, potentially through the modulation of glycolysis via the HIF-1 signaling pathway, thereby interfering with the progression of breast cancer pulmonary metastasis.
This research examined the molecular actions of acteoside, specifically its impact on the c-Jun N-terminal kinase (JNK) signaling pathway, in suppressing hepatoma 22(H22) tumors in a murine model. Fifty male BALB/c mice received subcutaneous H22 cell inoculations, subsequently stratified into groups: acteoside low-dose, acteoside medium-dose, acteoside high-dose, and cisplatin. Each group's administrative period encompassed two weeks, with five days of consecutive activity occurring within each week. A comprehensive assessment of the general condition of mice in each group was performed, evaluating factors such as mental status, dietary intake, water intake, activity levels, and fur characteristics. Before and after treatment, body weight, tumor volume, tumor weight, and the rate of tumor inhibition were evaluated and compared. Hematoxylin and eosin (HE) staining was used to study morphological changes in liver cancer tissues, followed by immunohistochemical and Western blot assays to detect the expression of phosphorylated JNK (p-JNK), JNK, Bcl-2, Beclin-1, and light chain 3 (LC3) in each tissue sample. mRNA expression of JNK, Bcl-2, Beclin-1, and LC3 was evaluated using the qRT-PCR technique. Microbiology education Sadly, mice receiving model and low-dose acteoside treatments presented with poor general conditions, a scenario starkly different from the noticeable improvement in the three remaining groups. The body weight of mice in the groups receiving medium-dose acteoside, high-dose acteoside, and cisplatin was significantly smaller than that of the model group (P < 0.001). The tumor volume in the model group presented no significant difference relative to the low-dose acteoside group, and the volume in the cisplatin group did not differ significantly from that of the high-dose acteoside group. Compared to the model group, the tumor volume and weight were markedly reduced in the medium-dose acteoside, high-dose acteoside, and cisplatin treatment groups, demonstrating a statistically significant difference (P < 0.0001). The percentage of tumor inhibition observed in the low-dose, medium-dose, and high-dose acteoside groups and the cisplatin group were 1072%, 4032%, 5379%, and 5644%, respectively. Analysis of HE staining showed a progressive decrease in the count of hepatoma cells and a corresponding escalation of cell necrosis in the acteoside and cisplatin groups. This effect was most conspicuous in the high-dose cohorts of the acteoside and cisplatin treatments. Acteoside and cisplatin treatment resulted in an upregulation of Beclin-1, LC3, p-JNK, and JNK expression, as determined by immunohistochemistry (P<0.05). In the medium-dose and high-dose acteoside groups, and the cisplatin group, Bcl-2 expression was decreased, according to the combined results of immunohistochemistry, Western blot, and quantitative real-time PCR (qRT-PCR) analyses (P<0.001). The expression of Beclin-1, LC3, and p-JNK protein was found to be elevated in the acteoside and cisplatin treated groups (P<0.001), according to Western blot results. There was no variation in JNK expression levels among the groups. qRT-PCR data showed a rise in Beclin-1 and LC3 mRNA levels in the acteoside and cisplatin treatment groups (P<0.05). A significant increase in JNK mRNA was found in the medium-dose and high-dose acteoside, and cisplatin groups (P<0.0001). In H22 mouse hepatoma cells, the upregulation of the JNK signaling pathway by acteoside fosters apoptosis and autophagy, thus limiting tumor progression.
The study explored decursin's influence on the proliferation, apoptosis, and migration of HT29 and HCT116 colorectal cancer cells within the context of the PI3K/Akt signaling pathway. Treatment of HT29 and HCT116 cells involved the use of decursin at concentrations of 10, 30, 60, and 90 mol/L. To examine the impact of decursin on HT29 and HCT116 cells, the following assays were employed: cell counting kit-8 (CCK8), cloning formation assays, Ki67 immunofluorescence, flow cytometry, wound healing assays, and Transwell assays, respectively, to assess cell survival, colony formation ability, proliferation, apoptosis, wound healing, and migration. The expression levels of epithelial cadherin (E-cadherin), neural cadherin (N-cadherin), vimentin, B-cell lymphoma/leukemia-2 (Bcl-2), Bcl-2-associated X protein (Bax), tumor suppressor protein p53, PI3K, and Akt were determined via Western blot. Conus medullaris Decursin, when contrasted with the control group, exhibited a substantial inhibitory effect on the proliferation and colony formation of HT29 and HCT116 cells, concurrently stimulating their apoptotic rate. This was accompanied by a substantial downregulation of Bcl-2 and a concomitant upregulation of Bax. Decursin's influence on wound healing and cellular migration was demonstrably negative, significantly reducing N-cadherin and vimentin expression, while concurrently elevating E-cadherin expression. Furthermore, a considerable decrease in the expression of PI3K and Akt was observed, and the expression of p53 was augmented. Decursin, in essence, may control epithelial-mesenchymal transition (EMT) by regulating the PI3K/Akt signaling pathway, thereby impacting the proliferation, apoptosis, and movement of colorectal cancer cells.
Using a mouse model of colitis-associated cancer (CAC), this study evaluated the effect of anemoside B4 (B4) on fatty acid metabolism. Using azoxymethane (AOM) and dextran sodium sulfate (DSS), the CAC model was created in mice. By random assignment, mice were divided into four categories: a normal group, a model group, and low-, medium-, and high-dose anemoside B4 groups. ReACp53 cell line The experiment's completion prompted a determination of the mouse colon's length and tumor size, and hematoxylin and eosin (H&E) staining was used to examine the colon for any pathological alterations. In order to analyze the spatial distribution of fatty acid metabolism-related substances within the colon tumor, samples from tissue slices were collected for metabolome analysis. The mRNA levels for SREBP-1, FAS, ACC, SCD-1, PPAR, ACOX, UCP-2, and CPT-1 were established using the method of real-time quantitative PCR (RT-qPCR). The results demonstrated that the model group exhibited reduced body weight (P<0.005) and colon length (P<0.0001), a greater number of tumors, and a higher pathological score (P<0.001). The spatial metabolome of colon tumors displayed a rise in the presence of fatty acids, their derivatives, carnitine, and phospholipid components. Significant increases (P<0.005, P<0.0001) in mRNA expression were observed via RT-qPCR for genes related to fatty acid synthesis and breakdown, such as SREBP-1, FASN, ACC, SCD-1, ACOX, UCP-2, and CPT-1.