Qingjie Fuzheng Granules regulates cancer cell proliferation, apoptosis and tumor angiogenesis in colorectal cancer xenograft mice via Sonic Hedgehog pathway

Zhu, Xiaodong; Yang, Hong; Mu, Lin; Shang, Haixia; Peng, Jun; Chen, Wu-Jin; Chen, Xuzheng; Lin, Jiumao

doi:10.21037/jgo-20-213

Cited by 12 publications

(9 citation statements)

References 48 publications

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“…Qinrui Han et al showed that bufarenogin induced intrinsic apoptosis through the cooperation of Bax and adenine nucleotide translocator ( Han et al, 2021 ). Xiao-Qin Zhu et al treated the CRC HCT-116 xenograft mouse model with Qingjie Fuzheng granules and found that this compound suppressed tumor cell proliferation through inhibiting the SHh pathway ( Zhu et al, 2020 ). Yang Li et al performed research on Gegen Qinlian decoction.…”

Section: Discussionmentioning

confidence: 99%

Disordered Gut Microbiota in Colorectal Tumor-Bearing Mice Altered Serum Metabolome Related to Fufangchangtai

Cai

Xiao²,

Lin³

et al. 2022

Front. Pharmacol.

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Purpose: This study aimed to investigate the relationship between gut microbiota (GM) and serum metabolism using antineoplastic Fufangchangtai (FFCT) as the model prescription in the treatment of colorectal cancer (CRC).Methods: Tumor-bearing mice and normal mice were administered different doses of FFCT. The tumor volume of tumor-bearing mice was observed. The levels of CD4+ and CD8+ T cells in the blood, spleen, and tumor of mice were determined using a flow cytometer. The bacterial microbiota in stool samples from mice and the serum metabolomics of FFCT-treated mice and fecal microbiota transplantation mice were detected using 16s RNA sequencing and liquid chromatography–mass spectrometry (LC/MS), respectively.Results: The tumor volume of mice showed no significant decrease after FFCT intervention. The levels of CD4+ and CD8+T lymphocytes showed a significant increase under the intervention of FFCT. GM of colorectal tumor-bearing mice and healthy mice were determined, and the diversity and abundance of Firmicutes, Deferribacteres, Bacteroidetes, and Proteobacteria were significantly different between the two groups. Furthermore, we found that the levels of matrine, isogingerenone B, and armillaripin were significantly decreased in tumor-bearing mice after FFCT intervention, indicating that the tumor-induced dysbiosis of gut bacteria may affect the absorption and metabolism of FFCT. Under the intervention of FFCT, serum metabolism of mice transplanted with feces from CRC patients showed less metabolites related to FFCT than that from healthy people, indicating that GM could be a single factor affecting the metabolism of FFCT. Furthermore, we found that different doses of FFCT-treated mice had higher abundance of Roseburia, Turicibacter, and Flexispira than that in the non-intervention control group. Firmicutes and Bacteroidetes in FFCT-treated groups showed a similar trend compared to the healthy group, indicating that FFCT might correct the intestinal microenvironment by modulating gut microbiota in colorectal tumor-bearing mice.Conclusion: The dysbiosis of GM in tumor-bearing mice reduced the serum metabolites related to FFCT, and FFCT could correct the disordered GM of colorectal tumor-bearing mice to exert efficacy.

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Section: Discussionmentioning

confidence: 99%

Disordered Gut Microbiota in Colorectal Tumor-Bearing Mice Altered Serum Metabolome Related to Fufangchangtai

Cai

Xiao²,

Lin³

et al. 2022

Front. Pharmacol.

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“…In the past few years, some researches have proved that Hedyotis diffusa Willd and Scutellaria barbata D. Don are capable of promoting apoptosis and inhibiting growth in varies types of cancer cells, including CRC [25,26]. In addition, previous in vitro and in vivo studies had proved that QFG can inhibit proliferation, migration, and invasion and induce apoptosis in cancer cells [6][7][8][9]. However, no studies have not been reported on the effect and mechanism of QFG on CRC cell autophagy and EMT which are also the key regulatory factors in the progression of CRC.…”

Section: Discussionmentioning

confidence: 99%

“…Qingjie Fuzheng granules (QFG), which belong to a traditional Chinese medicine (TCM) formula, are clinically effective for CRC treatments with few adverse effects [4,5]. In our previous in vitro study, we demonstrated that QFG could inhibit CRC cell proliferation, migration, and invasion and promote CRC cell apoptosis [6][7][8][9]. Invasion and metastasis are important characteristics of malignant tumors, and EMT plays a crucial role in invasion and metastasis of cancer cells [10,11].…”

Section: Introductionmentioning

confidence: 99%

Qingjie Fuzheng Granule Inhibits EMT and Induces Autophagy in Colorectal Cancer via mTOR Signaling Pathways

Zhu

Chen

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Qingjie Fuzheng granule (QFG) is a traditional Chinese medicinal formula used extensively as an alternative medicine for cancer treatment, including colorectal cancer (CRC). But its pathological mechanism in CRC is unclear. To study antitumor treatment effects and mechanisms of QFG, we established a CRC HCT-116 xenograft mouse model and assessed QFG on EMT and autophagy progression in vivo. The mice were randomly divided into 2 groups (n = 10 each group) and treated with intragastric administration of 1 g/kg of QFG or saline 6 days a week for 28 days (4 weeks). Body weight was measured every other day with electronic balance. At the end of the treatment, the tumor weight was measured. Immunohistochemical (IHC) and western blot (WB) assay were used to detect the expression level of E-cadherin, N-cadherin, vimentin, and TWIST1 to evaluate the effect of QFG on tumor cell EMT progression. IHC and WB assay were also used to detect the expression level of beclin-1, LC3-II, and p62 to evaluate the effect of QFG on tumor cell autophagy progression. Furthermore, the expression level of relative proteins in mTOR pathway was detected by WB assay to investigate the mechanism of QFG effect on CRC. We discovered that QFG inhibited the rise of tumor weight while it had no effect on mice body weight, which proved that QFG could inhibit CRC growth progression without significant side effects in vivo. In addition, QFG treatment inhibited EMT and induced autophagy progression in CRC tumor cells, including that QFG upregulated the expression of E-cadherin, beclin-1, and LC3-II, but downregulated the expression of N-cadherin, vimentin, TWIST1, and p62. And, QFG decreased the ratio of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR, but increased the ratio of p-AMPK/AMPK. All findings from this research proved that QFG can induce autophagy and inhibit EMT progression in CRC via regulating the mTOR signaling pathway.

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“…Qinrui Han [24] et al, showed that bufarenogin induced intrinsic apoptosis through the cooperation of Bax and adenine-nucleotide translocator. Xiao-Qin Zhu [25] et al, treated CRC HCT-116 xenograft mouse model with Qingjie Fuzheng Granules and found that this compound suppressed tumor cell proliferation through inhibiting SHh pathway. Yang Li [26] Jiyoung Ahn [27] et al, tested the community of GM in a study of 47 CRC subjects and 94 control subjects.…”

Section: Discussionmentioning

confidence: 99%

Effect of Disordered Gut Microbiota on Serum Metabolome Alterations in Colorectal Tumor-Bearing Mice Under The Intervention of Fufangchangtai

Cai

Lin

Xiao

et al. 2021

Preprint

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Background: The occurrence and development of colorectal cancer is related to the compositional and functional variation of gut microbiota. Compared with healthy people, gut microbiota of patients with colorectal cancer is in disorder. Most traditional Chinese Medicine is effective by oral administration and has both anti-tumor effect and enteric microecological regulative effect. However, whether the dysbiosis of gut microbiota under tumor burden affects the serum metabolome of human body that related to traditional Chinese medicine is unclear. In this study, Fufangchangtai (FFCT) was chosen to be the model prescription to explore the correlation between gut microbiota and the serum metabolism related to FFCT in anti colorectal cancer treatment. Results: The gut microbiota between colorectal tumor-bearing mice and healthy mice were determined by 16S rRNA gene sequencing, showing quite differences between the two groups and suggesting that Firmicutes , Deferribacteres , Bacteroidetes and Proteobacteria were marked differential intestinal bacteria. The alternations in serum metabolome in the FFCT-treating tumor-bearing mice and simple FFCT-treating mice were detected using Liquid chromatogragh-mass spectrometer (LC/MS), showing significant differences between the two groups as well. Metabolites of FFCT like Citric acid, （±）12-HEPE, Cycloartanyl ferulate were much more in simple FFCT-treating mice, indicating that the present of tumor could affect the absorption and metabolism of FFCT. Additionally, these differential metabolites of FFCT involved in multiple pathways including the Alanine, aspartate and glutamate metabolism, Central carbon metabolism in cancer, Biosynthesis of amino acids. Different doses of FFCT were given to the tumor-bearing mice through oral administration, and the results of gut microbiota 16S rRNA gene sequencing showing that FFCT-treating groups has higher abundance of Firmicutes , Turicibacter and Roseburia than tumor-bearing group, moreover, the abundance of these bacteria was positively correlated to the drug concentration. Firmicutes and Bacteroidetes in FFCT-treating groups showed a similar trend with Healthy group, indicating the modulation of FFCT on gut microbiota of colorectal tumor-bearing mice.Conclusions: Collectively, we concluded that the dysbiosis of gut microbiota in tumor-bearing mice could affect the serum metabolome of human body that related to FFCT, and FFCT could correct the gut microbiota of colorectal tumor-bearing mice. It was pointed out that the GM should be concerned during the therapy of FFCT. The more healthier intestinal microenvironment was conductive to the better clinical curative effect.

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Qingjie Fuzheng Granules regulates cancer cell proliferation, apoptosis and tumor angiogenesis in colorectal cancer xenograft mice via Sonic Hedgehog pathway

Cited by 12 publications

References 48 publications

Disordered Gut Microbiota in Colorectal Tumor-Bearing Mice Altered Serum Metabolome Related to Fufangchangtai

Disordered Gut Microbiota in Colorectal Tumor-Bearing Mice Altered Serum Metabolome Related to Fufangchangtai

Qingjie Fuzheng Granule Inhibits EMT and Induces Autophagy in Colorectal Cancer via mTOR Signaling Pathways

Effect of Disordered Gut Microbiota on Serum Metabolome Alterations in Colorectal Tumor-Bearing Mice Under The Intervention of Fufangchangtai

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