Bone morphogenetic protein and activin membrane‑bound inhibitor overexpression inhibits gastric tumor cell invasion via the transforming growth factor‑β/epithelial‑mesenchymal transition signaling pathway

Yuan, Chunling; Liang, Rong; Liu, Zhi‐Hui; Li, Yongqiang; Luo, Xi; Ye, Jiazhou; Lin, Yan

doi:10.3892/etm.2018.6083

Cited by 6 publications

(7 citation statements)

References 48 publications

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“…Bambi overexpression was confirmed on the protein level by immunohistochemistry for breast carcinoma cells MDA-MB-231 and by flow cytometry for gastric carcinoma cells MKN28 (Figures 1 and 2). Recently, BAMBI overexpression was found to inhibit growth and metastasis of gastric cancer cells (23). Thus, our data suggest that PpIX reduces TGF-beta signaling and tumor cell growth.…”

Section: Tgf-beta Pathway Blocked By Increased Ppix Due To Silencing Of Fechsupporting

confidence: 60%

Novel Targets of Protoporphyrin-IX Determined By Gene Expression Analysis

Dai¹,

Kemmner²

2020

IJCOCR

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Treatment with 5-Aminolevulinic acid-mediated photodynamic therapy is a promising therapeutic option for various carcinomas. An appropriate photosensitizer for photodynamic therapy is protoporphyrin-IX (PpIX), a light sensitive metabolite of heme synthesis. Incorporation of iron into PpIX leading to heme is carried out by Ferrochelatase (FECH). Earlier, we described a significant down regulation of FECH mRNA-expression and enzyme activity in carcinoma cells leading to an endogenous accumulation of PpIX. How PpIX affects the cell metabolism has not been examined so far. Thus, we tried to identify novel targets of PpIX with regard to cell proliferation, apoptosis and invasion. Endogenous generation of PpIX was induced by silencing of FECH in breast carcinoma MDA-MB-231 cells using a specific siRNA. Successful silencing of FECH was confirmed by RT-PCR and induction of PpIX was assessed by flow cytometry for each experiment. Subsequently, gene expression was determined using Affymetrix GeneChip® Human Gene 1.0 ST. Validation of microarray data was achieved by quantitative RT-PCR. Expression of one of the newly discovered target genes, BAMBI, was assessed by immunohistochemistry. In addition, the effect of silencing of FECH was examined by functional studies of cell apoptosis, invasion and wound healing. According to the gene expression analysis, an enhancement of PpIX suppressed Hedgehog as well as TGF-beta signaling. Expression of HHIP, a negative regulator of the hedgehog pathway, was found to be strongly increased after silencing of FECH. With regard to TGF-beta signaling, expression of the signaling inhibitor SMAD7 was strongly upregulated while the positive mediators SMAD2 and SMAD4 were less expressed after silencing FECH. Similarly, apoptosis of tumor cells was promoted, probably due to an increased expression of the pro-apoptotic gene APAF1 and a reduced expression of anti-apoptotic protein API5. Moreover, a significantly reduced invasion capability after treatment of cells with FECH siRNA was found. Here, we report that an accumulation of PpIX due to silencing of FECH affects various pathways and promotes apoptosis of tumor cells in different ways. Thus, silencing of FECH might have a tumor-suppressive effect. The search for substances which block FECH activity in a direct way therefore might be of high relevance for future cancer therapy approaches.

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Section: Tgf-beta Pathway Blocked By Increased Ppix Due To Silencing Of Fechsupporting

confidence: 60%

Novel Targets of Protoporphyrin-IX Determined By Gene Expression Analysis

Dai¹,

Kemmner²

2020

IJCOCR

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“…In addition, there is a therapeutic effect on the development of prostate cancer [47]. Although the BAMBI protein has been studied in many diseases such as tumors and tissue fibrosis [48, 49], the influence of traditional Chinese medicine on BAMBI in BPH is poorly understood. In the present study, we found that BAMBI mRNA and protein were expressed in rat prostate specimens and upregulated with KQR treatment.…”

Section: Discussionmentioning

confidence: 99%

Kangquan Recipe Regulates the Expression of BAMBI Protein via the TGF-β/Smad Signaling Pathway to Inhibit Benign Prostatic Hyperplasia in Rats

Chen

Huang

Peng

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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Background. Kangquan Recipe (KQR) is a traditional Chinese medicine compound made by our research group for the treatment of benign prostatic hyperplasia (BPH). Whether KQR can treat BPH as a single drug or play a role in the treatment of BPH in combination therapy needs further study. Aim of the Study. To investigate the effect of KQR on the expression of TGF-β/Smad signaling pathway-related factors in rats with BPH. In-depth analysis revealed the relevant signal transduction mechanism by which KQR acts to treat BPH. Materials and Methods. Forty-eight male Sprague-Dawley rats were randomly divided into six groups of 8 rats each. In addition to the control group, 40 rats were castrated and then injected with testosterone propionate to form a prostatic hyperplasia model. After 30 days, three groups received different concentrations of KQR (14 g/kg, 7 g/kg, and 3.5 g/kg), and the finasteride group received 0.5 mg/kg finasteride. The BPH group and the control group received the same volume of saline. All groups were treated for a total of 30 days. Rat body weight, prostate volume, wet weight, index, histology, and the mRNA and protein levels of TGF-β, TGF-βR1, TGF-βR2, p-Smad2, p-Smad3, BAMBI, E-cadherin, and N-cadherin in the prostate tissue were measured after the end of treatment. Results. Compared with the control group, the BPH group had increased prostate wet weight, volume, and index, and the histology showed significant BPH. Compared with the BPH group, the three KQR groups and the finasteride group all had varying levels of reduction in the prostate wet weight, volume, and index of the prostate and varying degrees of improvement in the histological manifestations of BPH. KQR downregulates the mRNA and/or protein expression of TGF-β, TGF-βR1, TGF-βR2, p-Smad2, p-Smad3, and N-cadherin protein in prostate tissue and increases the mRNA and protein expression of BAMBI and E-cadherin protein. Conclusions. In the model of BPH induced by testosterone propionate after castration, KQR can inhibit the conduction of the TGF-β/Smad signaling pathway by upregulating the expression of BAMBI protein and reversing EMT in rat prostate tissue.

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“…Several factors that regulate TGF-β1 activity have been identified and are being investigated as potential anticancer molecules for the prevention of PM in GC. For example, bone morphogenic protein and activin membrane-bound inhibitor (BAMBI) inhibited the TGF-β/EMT signaling pathway and suppressed the invasiveness of gastric tumors [ 77 ]; ASPP2 inhibited TGF-β1-induced EMT in GC cells by inhibiting in them the phosphorylation and nuclear accumulation of Smad2/3 [ 78 ]; and Ki26894, a TβR-I kinase inhibitor showed a decrease in invasiveness and EMT in GC [ 79 ]. These results imply the possibility of promising drugs targeting TGF-β1.…”

Section: Multistep Processmentioning

confidence: 99%

Molecular Mechanisms and Potential Rationale of Immunotherapy in Peritoneal Metastasis of Advanced Gastric Cancer

Kang

Kim

2022

Biomedicines

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Peritoneal metastasis (PM) is one of the most frequent metastasis patterns of gastric cancer (GC), and the prognosis of patients with PM is very dismal. According to Paget’s theory, disseminated free cancer cells are seeded and survive in the abdominal cavity, adhere to the peritoneum, invade the subperitoneal tissue, and proliferate through angiogenesis. In these sequential processes, several key molecules are involved. From a therapeutic point of view, immunotherapy with chemotherapy combination has become the standard of care for advanced GC. Several clinical trials of newer immunotherapy agents are ongoing. Understanding of the molecular process of PM and the potential rationale of immunotherapy for PM treatment is necessary. Beyond understanding of the molecular aspect of PM, many studies have been conducted on the modality of treatment of PM. Notably, intraperitoneal approaches, including chemotherapy or immunotherapy, have been conducted, because systemic treatment of PM has limitations. In this study, we reviewed the molecular mechanisms and immunologic aspects of PM, and intraperitoneal approaches under investigation for treating PM.

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Bone morphogenetic protein and activin membrane‑bound inhibitor overexpression inhibits gastric tumor cell invasion via the transforming growth factor‑β/epithelial‑mesenchymal transition signaling pathway

Cited by 6 publications

References 48 publications

Novel Targets of Protoporphyrin-IX Determined By Gene Expression Analysis

Novel Targets of Protoporphyrin-IX Determined By Gene Expression Analysis

Kangquan Recipe Regulates the Expression of BAMBI Protein via the TGF-β/Smad Signaling Pathway to Inhibit Benign Prostatic Hyperplasia in Rats

Molecular Mechanisms and Potential Rationale of Immunotherapy in Peritoneal Metastasis of Advanced Gastric Cancer

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