Pien Tze Huang Targets Cancer Proliferation and Inhibits Growth of Patient-derived Organoid and Xenograft Tumors in Pancreatic Cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE249726 | GEO | 2023/12/12
REPOSITORIES: GEO
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Project description:Aim: The aim of this study is to explore the impact of Pien Tze Huang (PZH) on enhancing T cell cytotoxicity by modulating colorectal cancer stem cell (CRC-CSC) markers, programmed death protein ligand-1 (PD-L1), and the transcription factor signal transducer and activator of transcription 3 (STAT3) protein expression in vivo, ex vivo, and in vitro. Methods: HCT116, HCT15, and SW480 cell lines were subjected to treatment with PZH, followed by assessment of cell viability and stemness through CCK8 and spheroid formation assays. Western blot and immunofluorescence techniques were employed to evaluate the expression levels of stem cell markers (DCLK1, CD133, CD44, MET, and LGR5), PD-L1, and STAT3 across three CRC cell lines and five patient-derived organoids (PDOs). Flow cytometry and western blot analyses were utilized to validate T cell expansion from both donors and CRC patients. CRC cells and CRC-PDOs, pre-treated with PZH, were co-cultured with expanded T cells from both donor and autologous peripheral blood mononuclear cells (PBMCs) respectively. The viability of CRC cells and PDOs was evaluated through Calcein-AM staining to measure fluorescence intensity and cell count following co-culture. In the syngeneic MC38 C57BL/6 xenograft model, tumor growth curve and body weight were monitored subsequent to treatment with PZH, anti-PD-1, and PZH combined with anti-PD-1. Immunohistochemistry was performed to assess protein levels of CD133, CD44, STAT3, PD-L1, CD8, and IL-6R in tumor tissue. Results: The effectiveness of PZH in reducing CRC cell viability and suppressing stemness markers, such as LGR5, CD44, MET, DCLK1, and CD133, is evident. PZH also displayed inhibitory effects on tumorigenesis in five CRC-PDOs, with varying sensitivity across cases (3 sensitive and 2 less sensitive). Moreover, PZH enhanced the cytotoxicity of donor T cells against CRC cells and rectified the cytotoxic deficiency or bolstered the cytotoxicity of autologous T cells against CRC-PDOs by downregulating PD-L1 and STAT3 protein expressi Conclusion: PZH enhances T cell-mediated killing effect by inhibiting CRC stem cell markers, PD-L1, and STAT3. Key Words: Pien Tze Huang, patient-derived organoid, colorectal cancer stem cells, programmed death protein ligand-1, signal transducer and activator of transcription 3
2024-05-06 | GSE265991 | GEO
Project description:In this study, we investigated the impact of PZH on inducing reactive oxygen species (ROS) to inhibit colorectal cancer (CRC) growth. CRC cell line HCT116 was exposed to PZH for 24 hours, then RNA-Sequencing was conducted and showed that PZH modulated ROS-related signaling pathways, including DNA repair and the unfolded protein response, concomitant with the suppression of proliferation-related genes such as PCNA and Ki-67.
2023-10-19 | GSE245680 | GEO
Project description:Purpose: We investigate the regulation circRNAs in the damaged fibrotic liver treated with Pien Tze Huang (PZH) by RNA-seq. Methods: Liver tissue circRNAs expression profiles from 8-week carbon tetrachloride (CCl4)-induced, and PZH-treated and CCl4-induced liver fibrosis control mice were investigated by RNA-seq and dysregulated circRNAs in PZH-treated were identified. Various bioinformatics analyses established competing endogenous RNA (ceNRA) in circRNAs-miRNAs-mRNAs axis. Moreover, GO annotation and Kegg pathway were analyzed to identify the relational biological processes and pathway. qRT–PCR validation was performed using LX-2 cell sample pairs and SYBR Green assays. Results: We identified 91 differentially expressed circRNAs in the PZH-treated compared with control mice, of which 58 up-regulated circRNAs and 43 down-regulated circRNAs. The ceRNA network were constructed suggesting the potential role of circRNAs is the regulation of target gene expression as a miRNAs sponge. Moreover, GO and Kegg pathway analysis showed that these predicted mRNAs were related to liver fibrosis-related pathways such as TNF, PI3K-Akt, and MAPK signaling pathway. Meanwhile, the results of validation qRT-PCR of target genes in LX-2 cells were in accordance with RNA-seq with high confidence. Conclusions: We identified the dysregulated circRNAs and established functional network of circRNA-miRNA-mRNA to further reveal the potential interactions and biological processes in PZH-treated liver fibrosis mice. These findings indicate that mmu_circ_Slc25a25 may modulate the transcription of certain genes, such as Slc7a11 and Slc39a14, which may provide a more precise and comprehensive perspective for clarifying the role of PZH therapy as a potential agent for treatment of liver fibrosis.
2021-03-01 | GSE150883 | GEO
Project description:Pien Tze Huang (PZH) is a traditional Chinese medicinal formula that has been extensively used in Asia for the treatment of liver diseases. We created two groups of liver cancer mouse models induced by carbon tetrachloride (CCl4): one group received treatment with PZH and the other did not receive any treatment. In the non-PZH treated group, we observed a significant increase in liver function indices including albumin (ALB), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Histological examination using hematoxylin and eosin (HE) staining revealed inflammation around the hepatic vein in the non-PZH treated group. Furthermore, Masson's trichrome staining demonstrated the presence of blue-stained collagen fibers around the hepatic vein in the non-PZH treated group. These findings suggest that PZH may have therapeutic effects on liver inflammation and cancer. To further explore the molecular mechanisms of PZH's action, we conducted mRNA, long non-coding RNA (lncRNA), circular RNA (circRNA), and microRNA (miRNA) sequencing to identify potential drug targets at the transcriptome level. We identified 478 differentially expressed protein-coding transcripts and 68 differentially expressed lncRNA transcripts. Our study provides insights into potential transcriptional therapeutic targets for the clinical use of PZH in treating liver diseases.
2024-05-26 | GSE268337 | GEO
Project description:Pien Tze Huang (PZH) is a traditional Chinese medicine which was widely utilized in Asia for hepatic diseases. We construct two groups hepatic fibrosis mice model using CCl4, one group using PZH treatment and another group didn’t treatment. We found that the liver functional indices including ALB, ALT and AST were significantly increased in non-PZH treatment group. HE staining showed that inflammation was emerged surrounding the hepatic vein in the non-PZH treatment group, Masson staining revealed that there are blue collagenous fibre surrounding hepatic vein in the non-PZH treatment group, this result indicated that PZH cured the hepatic inflammation and fibrosis. We performed the mRNA and LncRNA sequencing aim to explore the drug target using PZH treatment on transcriptome level. 905 protein coding transcripts and 23 lncRNA transcripts were differentially expressed. Our research provided potential transcriptional therapeutic target for the clinical treatment using PZH.
2019-12-18 | GSE133481 | GEO
Project description:Pien Tze Huang (PZH) is a traditional Chinese medicinal formula that has been extensively used in Asia for the treatment of liver diseases. We created two groups of liver cancer mouse models induced by carbon tetrachloride (CCl4): one group received treatment with PZH and the other did not receive any treatment. In the non-PZH treated group, we observed a significant increase in liver function indices including albumin (ALB), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Histological examination using hematoxylin and eosin (HE) staining revealed inflammation around the hepatic vein in the non-PZH treated group. Furthermore, Masson's trichrome staining demonstrated the presence of blue-stained collagen fibers around the hepatic vein in the non-PZH treated group. These findings suggest that PZH may have therapeutic effects on liver inflammation and cancer. To further explore the molecular mechanisms of PZH's action, we conducted mRNA, long non-coding RNA (lncRNA), circular RNA (circRNA), and microRNA (miRNA) sequencing to identify potential drug targets at the transcriptome level. We identified 478 differentially expressed protein-coding transcripts and 68 differentially expressed lncRNA transcripts. Our study provides insights into potential transcriptional therapeutic targets for the clinical use of PZH in treating liver diseases.
2024-05-26 | GSE268336 | GEO
Project description:Pien Tze Huang (PZH) is herbal traditional Chinese medicine which was widely utilized in Asia for hepatic diseases. We constructed two groups hepatic fibrosis mice model using CCl4, one group using PZH treatment and another group replacing PZH with double distilled water. All 12 mice were fed for 8 weeks and then killed to have their liver tissue taken out. Small RNA-seq were used to identify miRNAs of PZH medicine effect for hepatic fibrosis. We found the expression of these miRNAs (mmu-miR-205-5p, mmu-miR-3064-5p, mmu-miR-205-5p, mmu-miR-370-3p, mmu-miR-665-3p) were changed in PZH medicine treatment for hepatic fibrosis study. Furthermore, Hmga2 and Fgf9, miRNAs corresponding target genes (Sp4, Slc2a6, Tln2, Hmga2, Ank3, Pax9, Fgf9), have been reported association with hepatic fibrosis.
2021-06-28 | GSE137100 | GEO
Project description:Pien Tze Huang (PZH) is a traditional Chinese medicine which was widely utilized in Asia for hepatic diseases. We construct two groups liver cancer mice model using CCl4, one group using PZH treatment and another group didn?t treatment. We found that the liver functional indices including ALB, ALT and AST were significantly increased in non-PZH treatment group. HE staining showed that inflammation was emerged surrounding the hepatic vein in the non-PZH treatment group, Masson staining revealed that there are blue collagenous fibre surrounding hepatic vein in the non-PZH treatment group, this result indicated that PZH cured the hepatic inflammation and cancer. We performed the mRNA,LncRNA,ciecRNA and miRNA sequencing aim to explore the drug target using PZH treatment on transcriptome level. 478 protein coding transcripts and 68 lncRNA transcripts were differentially expressed. Our research provided potential transcriptional therapeutic target for the clinical treatment using PZH.
2024-05-26 | GSE268335 | GEO
Project description:We aimed to evaluate anti-cancer efficacy of Pien-Tze-Huang (PZH), and to investigate the underlying mechanisms by integrating transcriptional regulatory network analysis and experimental validation.
2022-12-31 | GSE221790 | GEO
Project description:Hepatic fibrosis is a spontaneous wound-healing response triggered by chronic liver injury. Pien Tze Huang (PZH), a traditional Chinese herbal medicine, has been widely used to treat various hepatic diseases in Asia. We used a CCl4-induced mouse model to establish a PZH group of hepatic fibrosis mice treated with PZH and a control group of hepatic fibrosis mice without any treatment. We performed RNA-seq and mass spectrometry sequencing to investigate the mechanism of the PZH response in hepatic fibrosis and identified multiple differentially expressed transcripts (DETs) and proteins (DEPs) that may be drug targets of PZH. Liver functional indices, including serum albumin (ALB), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were significantly decreased in the PZH treatment group (P < 0.05) in the eighth week. Hematoxylin-eosin (HE), Masson and Sirius red staining demonstrated that PZH significantly inhibited infiltration of inflammatory cells and collagen deposition. A total of 928 transcripts and 138 proteins were differentially expressed in PZH-treated mice compared to the control group. Gene Ontology (GO) enrichment analysis suggested that PZH may alleviate liver injury and fibrosis by enhancing the immune process. Taken together, our results revealed that multiple DETs and DEPs may serve as drug targets of PZH in hepatic fibrosis patient in future clinical practice.
| S-EPMC8379174 | biostudies-literature