Morphine promotes angiogenesis by activating PI3K/Akt/HIF-1α pathway and upregulating VEGF in hepatocellular carcinoma

Wang, Zhiyao; Jiang, Linghui; Wang, Jie; Chai, Zong‐Tao; Xiong, Wanxia

doi:10.21037/jgo-20-394

Cited by 18 publications

(11 citation statements)

References 41 publications

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“…Nearly half of the significant biological processes and pathway terms were intimately linked with the initiation and development of a wide type of human cancers [ 26 – 34 ]. Specifically, the contribution of angiogenesis, MAPK cascade and humoral immune response to the malignant process of HCC has been recorded in previous literature studies [ 35 – 37 ]. The serological testing and immunoblot assay by M Volkmann et al revealed humoral immune response to p53 exclusively in HCC patients and the presence of p53 antibodies in HCC patients was not dependent on alpha-fetoprotein level [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

“…HCC is rich in blood supply, and angiogenesis was indispensable for tumor growth, invasion and metastasis [ 41 ]. The work of Wang et al disclosed that morphine could induce angiogenesis in HCC through activating PI3K/Akt/HIF-1α pathway and up-regulating VEGF expression [ 37 ]. Despite there have been no studies on the parts of ACP6 in activities of the above mentioned biological processes and pathways, the analysis results in this study provided potential presumptions of the molecular mechanism of ACP6 in HCC.…”

Section: Discussionmentioning

confidence: 99%

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The expression characteristics and clinical significance of ACP6, a potential target of nitidine chloride, in hepatocellular carcinoma

Xiong

Yang

et al. 2022

BMC Cancer

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Background Acid phosphatase type 6 (ACP6) is a mitochondrial lipid phosphate phosphatase that played a role in regulating lipid metabolism and there is still blank in the clinico-pathological significance and functional roles of ACP6 in human cancers. No investigations have been conducted on ACP6 in hepatocellular carcinoma (HCC) up to date. Methods Herein, we appraised the clinico-pathological significance of ACP6 in HCC via organizing expression profiles from globally multi-center microarrays and RNA-seq datasets. The molecular basis of ACP6 in HCC was explored through multidimensional analysis. We also carried out in vitro and in vivo experiment on nude mice to investigate the effect of knocking down ACP6 expression on biological functions of HCC cells, and to evaluate the expression variance of ACP6 in xenograft of HCC tissues before and after the treatment of NC. Results ACP6 displayed significant overexpression in HCC samples (standard mean difference (SMD) = 0.69, 95% confidence interval (CI) = 0.56–0.83) and up-regulated ACP6 performed well in screening HCC samples from non-cancer liver samples. ACP6 expression was also remarkably correlated with clinical progression and worse overall survival of HCC patients. There were close links between ACP6 expression and immune cells including B cells, CD8 + T cells and naive CD4 + T cells. Co-expressed genes of ACP6 mainly participated in pathways including cytokine-cytokine receptor interaction, glucocorticoid receptor pathway and NABA proteoglycans. The proliferation and migration rate of HCC cells transfected with ACP6 siRNA was significantly suppressed compared with those transfected with negative control siRNA. ACP6 expression was significantly inhibited by nitidine chloride (NC) in xenograft HCC tissues. Conclusions ACP6 expression may serve as novel clinical biomarker indicating the clinical development of HCC and ACP6 might be potential target of anti-cancer effect by NC in HCC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The expression characteristics and clinical significance of ACP6, a potential target of nitidine chloride, in hepatocellular carcinoma

Xiong

Yang

et al. 2022

BMC Cancer

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“…The whole protein extraction kit was used to extract the total protein of the cell samples, and the BCA protein content detection kit was used to determine the protein concentration of each sample according to the instructions of the manufacturer. Western blot analysis was performed as described previously (30). The imaging was performed using the G:BOXChemiXR5 (Syngene, UK) gel imaging system.…”

Section: Protein Sample Preparation and Western Blotmentioning

confidence: 99%

c-MYC and HIF1α promoter G-quadruplexes dependent metabolic regulation mechanism of berberine in colon cancer

Wen¹,

Han²,

Li³

et al. 2022

J Gastrointest Oncol

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Background: G-quadruplexes are molecular switches regulating gene transcription. c-MYC and hypoxiainducible factor 1-alpha (HIF1α) play important roles in cell proliferation, apoptosis, and metabolic regulation in colon cancer. Whether berberine can regulate metabolism by interacting with c-MYC and HIF1α G-quadruplexes in colon cancer needs to be explored. Methods: The binding mode of berberine with c-MYC and HIF1α G-quadruplexes were explored by ultraviolet and visible absorption spectroscopy and fluorescence spectroscopy. Circular dichroism (CD) spectroscopy was performed to evaluate the effects of berberine on the stability of c-MYC and HIF1α G-quadruplexes. After different concentrations of berberine acting on HCT116 cells for 24 h, cell proliferation and apoptosis were detected by MTT assay and flow cytometry; quantitative real-time polymerase chain reaction and western blot were performed to detect mRNA and protein expression of c-MYC and HIF1α; transcriptome sequencing was used to analyze the metabolic pathways. For the effects of berberine on colon cancer mouse model with dose of 50 mg•kg −1 for 14 days, tumor growth were monitored, hematoxylin and eosin staining and immunofluorescence staining were performed to analyze histopathology and protein expression of c-MYC and HIF1α, central carbon metabolism was detected in tumor tissues. Results: The binding ability of berberine with c-MYC G-quadruplex was different to that of berberine with HIF1α G-quadruplex. Both binding modes involved π-π stacking. The stoichiometric ratios were 1:1, 1:3, and 3:1 for berberine with c-MYC G-quadruplex and only 1:1 for berberine with HIF1α G-quadruplex. Temperature had a greater effect on the binding of berberine to c-MYC G-quadruplex. Berberine could improve the thermal stability of both c-MYC and HIF1α G-quadruplexes. Berberine inhibited the gene transcription and protein expression of c-MYC and HIF1α in colon cancer HCT116 cells. In vivo, berberine delayed tumor progression and inhibited the protein expression of c-MYC and HIF1α. Twelve differential metabolites such as decreased adenosine triphosphate were obtained, indicating that berberine could regulate the metabolic pathways of the tricarboxylic acid (TCA) cycle and glycolysis/gluconeogenesis, among others. Conclusions: Berberine may inhibit colon cancer by regulating the TCA cycle and glycolysis/ gluconeogenesis based on the interaction with c-MYC and HIF1α G-quadruplexes.

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“…JAK2 activation by morphine has also been described to upregulate the phosphoinositol-3-kinase (PI3K)/Akt (protein kinase B) pathway [ 165 , 173 ]. This cycle-regulating pathway is induced by a variety of growth signals such as insulin, EGF, and calmodulin (upregulated directly by MOR activation), whereby activated PI3K phosphorylates and activates Akt, which can then activate factors such as mTOR [ 174 ] and eNOS [ 175 ].…”

Section: Vitamin C and Mor: Potential For Crosstalkmentioning

confidence: 99%

Opioids and Vitamin C: Known Interactions and Potential for Redox-Signaling Crosstalk

2022

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Opioids are among the most widely used classes of pharmacologically active compounds both clinically and recreationally. Beyond their analgesic efficacy via μ opioid receptor (MOR) agonism, a prominent side effect is central respiratory depression, leading to systemic hypoxia and free radical generation. Vitamin C (ascorbic acid; AA) is an essential antioxidant vitamin and is involved in the recycling of redox cofactors associated with inflammation. While AA has been shown to reduce some of the negative side effects of opioids, the underlying mechanisms have not been explored. The present review seeks to provide a signaling framework under which MOR activation and AA may interact. AA can directly quench reactive oxygen and nitrogen species induced by opioids, yet this activity alone does not sufficiently describe observations. Downstream of MOR activation, confounding effects from AA with STAT3, HIF1α, and NF-κB have the potential to block production of antioxidant proteins such as nitric oxide synthase and superoxide dismutase. Further mechanistic research is necessary to understand the underlying signaling crosstalk of MOR activation and AA in the amelioration of the negative, potentially fatal side effects of opioids.

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Morphine promotes angiogenesis by activating PI3K/Akt/HIF-1α pathway and upregulating VEGF in hepatocellular carcinoma

Cited by 18 publications

References 41 publications

The expression characteristics and clinical significance of ACP6, a potential target of nitidine chloride, in hepatocellular carcinoma

The expression characteristics and clinical significance of ACP6, a potential target of nitidine chloride, in hepatocellular carcinoma

c-MYC and HIF1α promoter G-quadruplexes dependent metabolic regulation mechanism of berberine in colon cancer

Opioids and Vitamin C: Known Interactions and Potential for Redox-Signaling Crosstalk

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