Inhibition to Epithelial-Mesenchymal Transition and Metastatic Potential In Colorectal Cancer Cell By Combination of Traditional Chinese Medicine Formulation Jiedu Sangen Decoction and PD-L1 Inhibitor

Shan, Feiyu; Sun, Leitao; Zhang, Leyin; Guo, Kaibo; Yan, Qingying; Feng, Guosheng; Zhu, Ying; Shen, Minhe; Ruan, Shanming

doi:10.1177/1534735420972486

Cited by 8 publications

(8 citation statements)

References 58 publications

(85 reference statements)

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“…It has been reported that PD-L1 mediates EMT through inhibition and degradation of Snail. Moreover, treatment with PD-L1 inhibitor sufficiently suppressed the migratory activity through modulating EMT and survival pathway [ 76 ]. Thus, the benefits of plant-produced anti-PD-L1, especially on sensitizing anoikis presented in this study would strengthen the possibility of using plants as an alternative production host to meet the therapeutic requirements globally at economical costs.…”

Section: Discussionmentioning

confidence: 99%

Expression of plant-produced anti-PD-L1 antibody with anoikis sensitizing activity in human lung cancer cells via., suppression on epithelial-mesenchymal transition

Phetphoung

Malla²,

Rattanapisit³

et al. 2022

PLoS ONE

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Immune checkpoint antibodies in cancer treatment are receptor-ligand pairs that modulate cancer immunity. PD-1/PD-L1 pathway has emerged as one of the major targets in cancer immunotherapy. Atezolizumab, the first anti-PD-L1 antibody approved for the treatment of metastatic urothelial, non-small cell lung, small cell lung and triple-negative breast cancers, is produced in Chinese Hamster Ovary (CHO) cells with several limitations i.e., high-production costs, low-capacity yields, and contamination risks. Due to the rapid scalability and low production costs, the transient expression in Nicotiana benthamiana leaves was investigated by co-infiltration of Agrobacterium tumefaciens GV3101 cultures harboring the nucleic acid sequences encoding for Atezolizumab heavy chain and light chain in this study. The transient expression of Atezolizumab in transformed N. benthamiana accumulated up to 86.76 μg/g fresh leaf weight after 6 days of agroinfiltration (OD 600 nm: 0.4) with 1:1 ratio of heavy chain to light chain. The structural and functional characteristics of plant-produced Atezolizumab was compared with commercially available Tecentriq® from CHO cells with similar binding efficacies to PD-L1 receptor. The direct anti-cancer effect of plant-produced anti-PD-L1 was further performed in human lung metastatic cancer cells H460 cultured under detachment condition, demonstrating the activity of anti-PD-L1-antibody on sensitizing anoikis as well as the suppression on anti-apoptosis proteins (Bcl-2 and Mcl-1) and modulation of epithelial to mesenchymal regulating proteins (E-cadherin, N-cadherin, Snail and Slug). In conclusion, this study manifests plants as an alternative cost-effective platform for the production of functional monoclonal antibodies for use in cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Expression of plant-produced anti-PD-L1 antibody with anoikis sensitizing activity in human lung cancer cells via., suppression on epithelial-mesenchymal transition

Phetphoung

Malla²,

Rattanapisit³

et al. 2022

PLoS ONE

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“…TCM has a unique advantage in anti-tumor metastasis and has been valued and affirmed by the medical community. The results have clarified that TCM compounds, such as Jiedu Sangen Decoction, Jianpi Yangzheng Xiaozheng Decoction, and Bu-Fei decoction, could weaken EMT to play the pharmacodynamic role of anti-tumor metastasis ( He et al, 2017 ; Wu et al, 2019 ; Shan et al, 2020 ). In the current study, the constituents of MSJZD were analyzed using the UPLC-Q-TOF-MS method.…”

Section: Discussionmentioning

confidence: 99%

Modified Sijunzi Decoction Inhibits Epithelial-Mesenchymal Transition of Non-Small Cell Lung Cancer by Attenuating AKT/GSK3β Pathway in vitro and in vivo

et al. 2022

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Modified Sijunzi Decoction (MSJZD) is an empirical prescription of Traditional Chinese Medicine (TCM) and has been corroborated to be effective in multiple human diseases, but its role in non-small cell lung cancer (NSCLC) is enigmatic. Here we mainly analyze the function and mechanism of MSJZD in NSCLC. In this study, we used a method that coupled ultra-performance liquid chromatography to quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) to investigate the major constituents in MSJZD with positive and negative ion modes. Additionally, in in vitro experiments, the effects of serum-containing MSJZD on the biological behavior of NSCLC cells induced by TGF-β1 were assessed by cell function experiments. Then, the influences of serum-containing MSJZD on epithelial-mesenchymal transition (EMT)-related markers were examined by immunofluorescence and western blot assays. Also, the AKT/GSK3β pathway and apoptosis-related markers were estimated by western blotting. Tumor xenografts were generated by subcutaneously injecting A549 cells into BALB/c nude mice to determine the effects of MSJZD in vivo. We first analyzed the composition of MSJZD. In positive ion mode, 47 kinds of components were identified. In negative ion mode, 45 kinds of components were identified. We also found that TGF-β1 contributed to inducing cell morphological changes and EMT progression. In vitro, surprisingly, cell proliferation, migration as well as invasion in NSCLC cells induced by TGF-β1, could be weakened by serum-containing MSJZD, and apoptosis was intensified. Moreover, serum-containing MSJZD weakened EMT passage and AKT/GSK3β pathway activation and induced apoptosis-related markers in NSCLC cells triggered by TGF-β1. In vivo, we discovered that MSJZD attenuated the tumor growth, promoted histopathological damage, and induced apoptosis in A549 tumor-bearing mice. Importantly, MSJZD has also restrained the development of EMT, AKT/GSK3β pathway, and TGF-β1 expression levels in nude mice. These findings demonstrated that MSJZD significantly weakened NSCLC progression by modulating EMT and AKT/GSK3β pathway.

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“…The tumor volume was gauged every 3 days until the 21 th day. After 21 th day, the nude mice were euthanized by cervical dislocation with intraperitoneal anesthesia of 1% pentobarbital sodium (100 μ L, P-010, Supelco, USA) [ 18 ]. Finally, the tumor was removed and weighed.…”

Section: Methodsmentioning

confidence: 99%

BHLHE41 Overexpression Alleviates the Malignant Behavior of Colon Cancer Cells Induced by Hypoxia via Modulating HIF-1α/EMT Pathway

Chen

Dong

Wan

et al. 2022

Gastroenterology Research and Practice

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Objective. BHLHE41 has been shown to be a marker of tumorigenesis. Colon cancer (CC) is a common malignant tumor of colonic mucosa. This study mainly explored the mechanism of BHLHE41 in alleviating malignant behavior of hypoxia-induced CC cells. Methods. The levels of BHLHE41 in CC and normal cell lines were tested by Western blot and qRT-PCR. After, CC cells were subjected to hypoxia treatment and BHLHE41 overexpression transfection, and the BHLHE41 expression, the effect of BHLHE41 on CC cell viability, apoptosis, migration, and invasion and cell cycle were tested by qRT-PCR and relevant cell functional experiments. HIF-1α and epithelial-mesenchymal transition- (EMT-) related proteins were tested by Western blot. Moreover, CC tumor-bearing model was established in nude mice, and the effect of BHLHE41 on the tumor was evaluated by measuring the tumor volume and weight. Then, the expressions of BHLHE41 and EMT-related proteins were detected by immunohistochemistry and Western blot. Results. Western blot and qRT-PCR showed that BHLHE41 was lowly expressed in CC cells. BHLHE41 overexpression could inhibit the hypoxia-induced CC cell viability, migration, and invasion, induce apoptosis, and alter cell cycle. Besides, BHLHE41 overexpression could enhance the levels of E-cadherin but reduce the levels of HIF-1α, N-cadherin, vimentin, and MMP9 in hypoxia-induced CC cells. Moreover, BHLHE41 overexpression reduced tumor volume, weight, and EMT-related proteins levels in tumor tissues. Conclusions. BHLHE41 overexpression could mitigate the malignant behavior of hypoxia-induced CC via modulating the HIF-1α/EMT pathway.

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Inhibition to Epithelial-Mesenchymal Transition and Metastatic Potential In Colorectal Cancer Cell By Combination of Traditional Chinese Medicine Formulation Jiedu Sangen Decoction and PD-L1 Inhibitor

Cited by 8 publications

References 58 publications

Expression of plant-produced anti-PD-L1 antibody with anoikis sensitizing activity in human lung cancer cells via., suppression on epithelial-mesenchymal transition

Expression of plant-produced anti-PD-L1 antibody with anoikis sensitizing activity in human lung cancer cells via., suppression on epithelial-mesenchymal transition

Modified Sijunzi Decoction Inhibits Epithelial-Mesenchymal Transition of Non-Small Cell Lung Cancer by Attenuating AKT/GSK3β Pathway in vitro and in vivo

BHLHE41 Overexpression Alleviates the Malignant Behavior of Colon Cancer Cells Induced by Hypoxia via Modulating HIF-1α/EMT Pathway

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