Modulation of differentiation of rat granulosa cells in vitro by interferon-γ

1992 ◽  
Vol 133 (1) ◽  
pp. 131-139 ◽  
Author(s):  
S. Xiao ◽  
J. K. Findlay
Keyword(s):  
Granulosa Cell ◽  
Granulosa Cells ◽  
Cell Function ◽  
Inhibitory Effect ◽  
Interferon Γ ◽  
Detectable Effect ◽  
Aromatase Activity ◽  
Dependent Manner ◽  
Ifn Γ

ABSTRACT The effects of recombinant rat interferon-γ (rRaIFN-γ) and rat IFN (RaIFN, a mixture of IFN-γ and -α) on basal and FSH-induced ovarian granulosa cell function were studied. Granulosa cells were harvested from diethylstilboestrol-treated immature rats and cultured (2 × 105 viable cells/well per 0·5 ml) in serumfree medium with or without treatment for 48 h. In the presence of FSH (20 ng/ml), rRaIFN-γ (10–1000 U/ml) significantly inhibited FSH-stimulated aromatase activity (76·4 ± 2·3% maximum inhibition compared with FSH treatment alone), inhibin (40·4 ± 3·7%), progesterone (47·7 ± 8·6%) and 20α-hydroxypregn-4-en-3-one (20α-OHP) (51·8±1·7%) production in a dose-dependent manner. Furthermore, rRaIFN-γ inhibited FSH- and forskolin (FSK; 30 μmol/l)-induced extracellular cAMP accumulation (46·0 ± 6·6% and 29·1 ± 7·3% respectively). The inhibitory effect of rRaIFN-γ on FSK-induced cAMP was accompanied by decreased FSK-induced aromatase activity, inhibin, progesterone and 20α-OHP production. rRaIFN-γ had no detectable effect on aromatase activity, progesterone production and 20α-OHP production in the absence of FSH, but significantly stimulated basal inhibin production by 1·5-fold. rRaIFN-γ alone also caused a small but significant increase in basal levels of cAMP. The timecourse studies showed that FSH-induced aromatase activity and inhibin production were consistently suppressed by rRaIFN-γ, FSH-induced progesterone and 20α-OHP were inhibited at 1 and 2 days and then stimulated on days 3, 4 and 5 relative to FSH alone. There was no difference in DNA content between treatment and non-treatment wells during 5 days of culture. RaIFN had similar effects to rRaIFN-γ. We conclude that IFN-γ can inhibit FSH-induced granulosa cell differentiation and that, in the absence of FSH, IFN-γ stimulated undifferentiated granulosa cells to produce more inhibin. The mechanism of its action is likely to involve changes in cAMP production. Journal of Endocrinology (1992) 133, 131–139

scholarly journals SAT0363 DELPHINIDIN DOSE-DEPENDENTLY DIMINISHES PERIPHERAL IL-17 AND IFN-Γ PRODUCING LYMPHOCYTES IN PSORIATIC ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1128.1-1129
Author(s):  
A. Mavropoulos ◽  
S. Tsiogkas ◽  
D. Skyvalidas ◽  
C. Liaskos ◽  
A. Roussaki-Schulze ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Cell Viability ◽  
Annexin V ◽  
Nkt Cells ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Research Support ◽  
Research Activities ◽  
Ifn Γ

Background:Delphinidin, a dietary anthocyanidin and powerful anti-oxidant from pigmented fruits and vegetables, has broad anti-inflammatory properties. In a human skin model of psoriasis, delphinidin reduced expression of proliferative and inflammatory markers (1).Objectives:The rationale of our study was to assess whether delphinidin can in vitro suppress IL-17 and IFN-γ production in peripheral blood mononuclear cell (PBMC) subsets from patients with psoriatic arthritis (PsA).Methods:PBMCs were obtained from 24 patients with PsA attending the outpatient clinic of the Department of Rheumatology/clinical Immunology at the University General Hospital of Larissa, Greece. 16 age- and sex-matched healthy volunteers were also included in the study. Delphinidin was supplemented at a concentration ranging from 1 to 50μg/ml, one hour prior to cell stimulation. Cell viability (Annexin V staining) and innate/adaptive lymphocyte subpopulations were assessed by flow cytometry with a panel of fluorochrome-conjugated antibodies against CD56, CD3, CD4 and CD8. Intracellular expression of IL-17 and IFN-γ was measured following PMA/ionomycin stimulation for 5 hours using standard cell permeabilization protocols and monoclonal antibodies against IL-17 and IFN-γResults:Delphinidin at concentration ≥10 μg/ml sharply diminished IL-17-production by CD4(+) T cells (Th17) and CD56(+)CD3(+) (NKT) cells from patients with psoriatic arthritis and normal controls (p≤0.05). IFN-γ producing T (CD4 and CD8) cells, as well as NK and NKT cells were also dose-dependently suppressed following delphinidin pre-incubation in both patients and healthy controls. Inhibition of IFN-γ(+) cells ranged from 27 to 69% and peaked at delphinidin concentration 20-50μg/ml. The inhibitory effect of delphinidin on IL-17 and IFN-γ producing lymphocytes was not due to compromised cell viability, as assessed by annexin V binding.Conclusion:Delphinidin exerts, in a dose-dependent manner, a profound in vitro inhibitory effect on T cell and NKT cell IL-17 and IFN-γ production in PsA, and therefore, it may be used as a dietary immunosuppressant, complementary to standard treatment.References:[1]Chamcheu JC Skin Pharmacol Physiol. 2015;28(4):177-88. doi: 10.1159/000368445Disclosure of Interests:ATHANASIOS MAVROPOULOS: None declared, Sotirios Tsiogkas: None declared, Dimitrios Skyvalidas: None declared, Christos Liaskos: None declared, Aggeliki Roussaki-Schulze Grant/research support from: Received a grant to support the educational and research activities of the department from Genesis Pharma (2018), Speakers bureau: Received honoraria from Genesis Pharma and Janssen(2017) and from Roche and Pharmaserve Lilly(2018), Efterpi Zafiriou Speakers bureau: Received honoraria from Genesis Pharma, Abbvie, Novartis, Roche, Jansses(2017) and Novartis, Abbvie(2018), Dimitrios Bogdanos: None declared, Lazaros Sakkas Grant/research support from: Received a grant to support the educational and research activities of the department from Bristol-Meyers Squib, Speakers bureau: Received honoraria from Actellion(2018), Janssen(2017), Novartis(2017), Sanofi-Aventis(2018), Abbvie(2017) and Roche(2017)

scholarly journals The role of IGFs in the regulation of ovarian follicular growth in the brushtail possum (Trichosurus vulpecula)

Reproduction ◽  
2010 ◽  
Vol 140 (2) ◽  
pp. 295-303 ◽  
Author(s):  
Jennifer L Juengel ◽  
Lisa J Haydon ◽  
Brigitta Mester ◽  
Brian P Thomson ◽  
Michael Beaumont ◽  
...  
Keyword(s):  
Granulosa Cell ◽  
Granulosa Cells ◽  
Cell Function ◽  
Antral Follicle ◽  
Brushtail Possum ◽  
Follicular Growth ◽  
Theca Cells ◽  
Ovarian Follicular Growth

IGFs are known to be key regulators of ovarian follicular growth in eutherian mammals, but little is known regarding their role in marsupials. To better understand the potential role of IGFs in the regulation of follicular growth in marsupials, expression of mRNAs encoding IGF1, IGF2, IGF1R, IGF-binding protein 2 (IGFBP2), IGFBP4 and IGFBP5 was localized by in situ hybridization in developing ovarian follicles of the brushtail possum. In addition, the effects of IGF1 and IGF2 on granulosa cell function were tested in vitro. Both granulosa and theca cells synthesize IGF mRNAs, with the theca expressing IGF1 mRNA and granulosa cell expressing IGF2 mRNA. Oocytes and granulosa cells express IGF1R. Granulosa and theca cells expressed IGFBP mRNAs, although the pattern of expression differed between the BPs. IGFBP5 mRNA was differentially expressed as the follicles developed with granulosa cells of antral follicles no longer expressing IGFBP5 mRNA, suggesting an increased IGF bioavailability in the antral follicle. The IGFBP protease, PAPPA mRNA, was also expressed in granulosa cells of growing follicles. Both IGF1 and IGF2 stimulated thymidine incorporation but had no effect on progesterone production. Thus, IGF may be an important regulator of ovarian follicular development in marsupials as has been shown in eutherian mammals.

scholarly journals Effect ofTityus serrulatusvenom on cytokine production and the activity of murine macrophages

2002 ◽  
Vol 11 (1) ◽  
pp. 23-31 ◽  
Author(s):  
Vera L. Petricevich
Keyword(s):  
Cytokine Production ◽  
Peritoneal Macrophages ◽  
Interferon Γ ◽  
Enzyme Linked Immunosorbent Assay ◽  
No Production ◽  
Dependent Manner ◽  
Immune Functions ◽  
Macrophage Activity ◽  
Ifn Γ

The purpose of this study was to investigate the effects ofTityus serrulatusvenom (TSV) on murine peritoneal macrophages evaluated in terms of activation. The effects of crude TSV were analysed by detection of cytokines, oxygen intermediate metabolites (H2O2) and nitric oxide (NO) in supernatants of peritoneal macrophages. Several functional bioassays were employed including anin vitromodel for envenomating: cytotoxicity of TSV was assessed using the lyses percentage. Tumor necrosis factor (TNF) activity was assayed by measuring its cytotoxic activity on L-929 cells, and interleukin-6 (IL-6) and interferon-γ (IFN-γ) were assayed by enzyme-linked immunosorbent assay, whereas NO levels were detected by Griess colorimetric reactions in culture supernatant of macrophages incubated with TSV and subsequently exposed to either lipopolysaccharide or IFN-γ. Incubation of macrophages with TSV increased production of IL-6 and IFN-γ in a dose-dependent manner. TNF production was not detected in supernatants treated with TSV at any concentration. The increase in IL-6 secretion was not associated with concentration-dependent cytoxicity of TSV on these cells. These data suggest that the cytotoxicity does not appear to be the main cause of an increased cytokine production by these cells. Although NO is an important effector molecule in macrophage microbicidal activity, the inducing potential of the test compounds for its release was found to be very moderate, ranging from 125 to 800 mM. Interestingly, NO levels of peritoneal macrophages were increased after IFN-γ. Moreover, NO production had an apparent effect on macrophage activity. The results obtained here also shown that the TSV induces an important elevation in H2O2release. These results combined with NO production suggest that TSV possesses significant immunomodulatory activities capable of stimulating immune functionsin vitro.

scholarly journals Bone morphogenetic protein-6 enhances gonadotrophin-dependent progesterone and inhibin secretion and expression of mRNA transcripts encoding gonadotrophin receptors and inhibin/activin subunits in chicken granulosa cells

Reproduction ◽  
2007 ◽  
Vol 134 (2) ◽  
pp. 293-306 ◽  
Author(s):  
Sara L Al-Musawi ◽  
Richard T Gladwell ◽  
Philip G Knight
Keyword(s):  
Bone Morphogenetic Protein ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Cell Function ◽  
Dependent Manner ◽  
Cell Type ◽  
Inhibin A ◽  
Theca Cells ◽  
Subunit Mrna ◽  
Morphogenetic Protein

The aims were to examine ovarian expression of bone morphogenetic protein (BMP) ligands/receptor mRNAs in the chicken and to test the hypothesis that theca-derived BMP(s) modulates granulosa cell function in a paracrine manner. RT-PCR revealed expression of multiple BMPs in granulosa and theca cells from prehierarchical and preovulatory follicles with greater expression in theca cells; both cell types expressed BMP receptors-IA, -IB and -II consistent with tissue responsiveness. Preovulatory granulosa cells (F1, F2 and F3/4) were cultured with BMP-6 (expressed by theca but not granulosa) in the presence/absence of LH, FSH or 8-Br-cAMP. BMP-6 increased ‘basal’ and gonadotrophin-induced inhibin-A and progesterone secretion by each cell type but did not enhance the effect of 8-Br-cAMP. This indicates that the observed synergism between BMP-6 and gonadotrophin might involve BMP-induced up-regulation of gonadotrophin receptors. In support of this, BMP-6 alone increased LH-receptor (LHR) mRNA in F1 cells and FSH-receptor (FSHR) mRNA in F1, F2 and F3/4 cells. BMP-6 also enhanced LH/FSH-induced LHR transcript amount in each cell type but did not raise FSHR transcript amounts above those induced by BMP-6 alone. To further explore BMP-6 action on inhibin-A secretion, we quantified inhibin/activin subunits (α, βA, βB) mRNAs. Consistent with its effect on inhibin-A secretion, BMP-6 enhanced ‘basal’ expression of α- and βA-subunit mRNA in F1, F2 and F3/4 cells, and βB-subunit mRNA in F3/4 cells. BMP-6 markedly enhanced FSH/LH-induced expression of α-subunit in all follicles and FSH-induced βA-subunit in F2 and F3/4 follicles but not in F1 follicles. Neither BMP-6 alone, nor FSH/LH alone, affected ‘basal’ βB mRNA abundance. However, co-treatment with gonadotrophin and BMP-6 greatly increased βB-subunit expression, the response being lowest in F1 follicles and greatest in F3/4 follicles. Collectively, these results support the hypothesis that intraovarian BMPs of thecal origin have a paracrine role in modulating granulosa cell function in the chicken in a preovulatory stage-dependent manner.

Porcine granulosa cell conditioned media as autocrine regulator of progesterone secretion

1993 ◽  
Vol 5 (1) ◽  
pp. 95
Author(s):  
RT Denkova ◽  
IG Ivanov ◽  
LN Kanchev
Keyword(s):  
Granulosa Cell ◽  
Granulosa Cells ◽  
Cultured Cells ◽  
Primary Cultures ◽  
Inhibitory Effect ◽  
Conditioned Media ◽  
Progesterone Secretion ◽  
Porcine Granulosa Cells ◽  
Porcine Granulosa Cell

The ability of porcine granulosa cells to release a progesterone inhibiting substance(s) was examined in vitro. Granulosa cells (SGCs, MGCs and LGCs) were harvested from small, medium or large antral follicles respectively. The effect of granulosa cell conditioned media obtained from small follicles (SGCCM) was studied in the culture of LGCs by estimation of progesterone secretion; the conditioned media evoked the inhibition of progesterone secretion by the LGCs. SGCCM produced by various numbers of cultured granulosa cells showed a dose-related inhibition of progesterone production. A maximum inhibitory effect was noted when a 5-fold concentration of SGCCM was used. The addition of SGCCM had no effect on the growth of the cultured cells. The factor(s) inhibiting progesterone secretion appeared to be a nonsteroidal substance of molecular mass greater than 10 kDa and was heat-stable and trypsin-sensitive. The data presented support the suggestion that the conditioned media generated by primary cultures of SGCs contain nonsteroidal regulators capable of inhibiting progesterone secretion by cultured LGCs; this inhibitory activity can play an important autocrine regulatory role in the process of follicular differentiation.

Progesterone stimulates fibronectin production by chicken granulosa cells in vitro

1994 ◽  
Vol 130 (2) ◽  
pp. 159-165 ◽  
Author(s):  
Elikplimi K Asem ◽  
Michael D Conkright ◽  
Ruben P Novero
Keyword(s):  
Granulosa Cells ◽  
Follicular Development ◽  
Inhibitory Effect ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Ru 486 ◽  
Progesterone Synthesis ◽  
Exogenous Progesterone ◽  
Chicken Ovary

Asem EK, Conkright MD, Novero RP. Progesterone stimulates fibronectin production by chicken granulosa cells in vitro. Eur J Endocrinol 1994;130:159–65. ISSN 0804–4643 Experiments were conducted in vitro to examine the effect of progesterone on fibronectin production by chicken ovarian granulosa cells. Granulosa cells isolated from the largest (F1: mature) and third-largest (F3: developing) preovulatory follicles as well as from a pool of immature small yellow follicles (SYF) of the domestic chicken ovary were incubated in serum-free Medium-199 and the amounts of fibronectin and progesterone produced were quantified by enzyme-linked immunosorbent assay and radioimmunoassay, respectively. The amounts of basal fibronectin and progesterone produced by granulosa cells from F1, F3 and SYF follicles increased with advancing stages of follicular development. Thus, the quantity of basal fibronectin secreted by granulosa cells was directly proportional to the amount of progesterone produced by them. Exogenously supplied progesterone increased the amount of fibronectin secreted by F1 and F3 cells in a dose-dependent manner, but its effect on SYF cells was marginal. Cyanoketone (an inhibitor of progesterone synthesis) suppressed basal fibronectin production by F1 and F3 granulosa cells and its inhibitory action was reversed by exogenous progesterone. The progesterone antagonist RU 486 also attenuated basal fibronectin production by F1 and F3 granulosa cells, but only the highest concentration affected SYF cells. The inhibitory effect of RU 486 was diminished in the presence of exogenous progesterone. These data show that progesterone regulates fibronectin production by chicken granulosa cells. They suggest that in avian granulosa cells, endogenous progesterone can stimulate fibronectin synthesis in an intracrine or autocrine manner. EK Asem, Department of Physiology and Pharmacology, School of Veterinary Medicine, Purdue University, 1246 Lynn Hall, West Lafayette, IN 47907-1246. USA

scholarly journals Non-canonical progesterone signaling in granulosa cell function

Reproduction ◽  
2014 ◽  
Vol 147 (5) ◽  
pp. R169-R178 ◽  
Author(s):  
John J Peluso ◽  
James K Pru
Keyword(s):  
Granulosa Cell ◽  
Granulosa Cells ◽  
Polycystic Ovarian Syndrome ◽  
Cell Function ◽  
Reproductive Capacity ◽  
Dependent Manner ◽  
Follicle Growth ◽  
Altered Expression ◽  
Ovarian Syndrome ◽  
Enhancer Factor

It has been known for over 3 decades that progesterone (P4) suppresses follicle growth. It has been assumed that P4 acts directly on granulosa cells of developing follicles to slow their development, as P4 inhibits both mitosis and apoptosis of cultured granulosa cells. However, granulosa cells of developing follicles of mice, rats, monkeys, and humans do not express the A or B isoform of the classic nuclear receptor for P4 (PGR). By contrast, these granulosa cells express other P4 binding proteins, one of which is referred to as PGR membrane component 1 (PGRMC1). PGRMC1 specifically binds P4 with high affinity and mediates P4's anti-mitotic and anti-apoptotic action as evidenced by the lack of these P4-dependent effects in PGRMC1-depleted cells. In addition, mice in which PGRMC1 is conditionally depleted in granulosa cells show diminished follicle development. While the mechanism through which P4 activation of PGRMC1 affects granulosa cell function is not well defined, it appears that PGRMC1 controls granulosa cell function in part by regulating gene expression in T-cell-specific transcription factor/lymphoid enhancer factor-dependent manner. Clinically, altered PGRMC1 expression has been correlated with premature ovarian failure/insufficiency, polycystic ovarian syndrome, and infertility. These collective studies provide strong evidence that PGRMC1 functions as a receptor for P4 in granulosa cells and that altered expression results in compromised reproductive capacity. Ongoing studies seek to define the components of the signal transduction cascade through which P4 activation of PGRMC1 results in the regulation of granulosa cell function.

scholarly journals CXCL12 and its receptors regulate granulosa cell apoptosis in PCOS rats and human KGN tumor cells

Reproduction ◽  
2020 ◽  
Author(s):  
Ling Jin ◽  
Liang Ren ◽  
Jing Lu ◽  
Xue Wen ◽  
Siying Zhuang ◽  
...  
Keyword(s):  
Granulosa Cell ◽  
Granulosa Cells ◽  
Polycystic Ovary ◽  
Low Grade ◽  
Dependent Manner ◽  
Cxcr4 Antagonist ◽  
Concentration Dependent Manner ◽  
Apoptosis Rate

Polycystic ovary syndrome (PCOS) is a common endocrine disorder accompanied by chronic low-grade inflammation; its etiology is still undefined. This study investigated the expression of CXCL12, CXCR4, and CXCR7 in PCOS rats and their role in regulation of apoptosis. To accomplish this, we established an in vivo PCOS rat model and studied KGN cells (human ovarian granulosa cell line) in vitro. In PCOS rats, the ovarian expression of CXCL12, CXCR4, and CXCR7 was reduced, and the apoptosis rate of granulosa cells was increased, accompanied by decreased expression of BCL2 and increased expression of BAX and cleaved CASPASE3 (CASP3). We further showed that recombinant human CXCL12 treatment upregulated BCL2, downregulated BAX, and cleaved CASP3 in KGN cells to inhibit their apoptosis in a concentration-dependent manner; moreover, the effect of CXCL12 was weakened by CXCR4 antagonist AMD3100 and anti-CXCR7 neutralizing antibody. In conclusion, PCOS rats showed decreased CXCL12, CXCR4, and CXCR7 expression and increased apoptosis rate of ovarian granulosa cells. Further, in human KGN cells, CXCL12 regulated the expression of BAX, BCL2, and cleaved CASP3 to inhibit apoptosis through CXCR4- and CXCR7-mediated signal transmission. These findings may provide a theoretical and practical basis for illuminating the role of proinflammatory cytokines in the pathogenesis of PCOS.

Control of inhibin production by primate granulosa cells

1989 ◽  
Vol 123 (1) ◽  
pp. 65-73 ◽  
Author(s):  
S. G. Hillier ◽  
E. J. Wickings ◽  
P. T. K. Saunders ◽  
A. F. Dixson ◽  
S. Shimasaki ◽  
...  
Keyword(s):  
Granulosa Cell ◽  
Granulosa Cells ◽  
Follicular Development ◽  
Common Marmoset ◽  
Dependent Manner ◽  
Stimulatory Action ◽  
Α Subunit ◽  
Luteal Tissue ◽  
Ovarian Inhibin

ABSTRACT In-vitro data from experiments on rats implicate granulosa cells as primary sites of hormone-dependent ovarian inhibin biosynthesis, but no equivalent data exist for primates. We have used the common marmoset (Callithrix jacchus) to investigate inhibin biosynthesis in primate granulosa cells in vitro and to determine its relationship to preovulatory follicular development. To relate the production of immunoactive inhibin to follicular maturity, we studied primary granulosa cell cultures from follicles at progressive stages of preovulatory development. Granulosa cells from 'large' (≥2·0 mm diameter) follicles expressed high rates of inhibin production and steroidogenesis (progesterone), and were positively regulated by human (h)LH in vitro. Less mature granulosa cells from 'medium' (1·1–1·9 mm) and 'small' (≤ 1·0 mm) follicles expressed proportionately lower rates of inhibin production and steroidogenesis, but each parameter was stimulated in a dose- and time-dependent manner by hFSH in vitro. The stimulatory action of hFSH on immunoactive inhibin was augmented by the presence of testosterone or oestradiol; testosterone (but not oestradiol) also augmented the steroidogenic response to hFSH. Marmoset luteal tissue also produced inhibin in vitro and expressed an ∼1·5 kb inhibin α-subunit mRNA, confirming the corpus luteum as a source of ovarian inhibin in primates. These results provide direct experimental evidence that primate granulosa cells produce inhibin. They suggest that production of inhibin by immature granulosa cells is initially induced by FSH and subject to modulation by follicular steroids. During advanced preovulatory development, granulosa cell inhibin production becomes directly responsive to LH, thereby indicating a role for LH in the control of peri- and postovulatory inhibin secretion by the primate ovary. Journal of Endocrinology (1989) 123, 65–73

scholarly journals Cynaropicrin Shows Antitumor Progression Potential in Colorectal Cancer Through Mediation of the LIFR/STATs Axis

2021 ◽  
Vol 8 ◽  
Author(s):  
Dandan Zheng ◽  
Yu Zhu ◽  
Yili Shen ◽  
Sisi Xiao ◽  
Lehe Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Western Blotting ◽  
Cell Function ◽  
Xenograft Model ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Leukemia Inhibitory Factor Receptor ◽  
Antitumor Effects

BackgroundColorectal cancer (CRC) is the second deadliest malignant disease in the world and the leukemia inhibitory factor receptor/signal transducers and activators of transcriptions (LIFR/STATs) signaling axis plays an important role in the molecular biology of CRC.MethodsCell function tests were performed to observe the inhibitory effect of cynaropicrin on human CRC cells (RKO, HCT116, and DLD-1). Expression levels of LIFR, P-STAT3, P-STAT4, and apoptotic proteins were detected by Western blotting. Immunoprecipitation confirmed the presence of LIFR/STAT3/STAT4 complex. Cell immunofluorescence assay was used to observe the subcellular localization of STAT3 and STAT4. In vivo efficacy of cynaropicrin was evaluated by a xenotransplantation model in nude mice.ResultsCynaropicrin significantly reduced the survival ability of human CRC cells and promoted apoptosis in a dose-dependent manner. Western blotting results suggested that the antitumor effects of cynaropicrin might be mediated by inhibition of the LIFR/STATs axis. Cynaropicrin reduced the formation of STAT3/STAT4 heterodimers and blocked their entry into the nucleus. Cynaropicrin also suppressed tumor growth in the xenograft model.ConclusionThe results showed that cynaropicrin exerted a strong inhibitory effect on CRC in vitro and in vivo. Our study concluded that cynaropicrin has potential application prospects in the field of anti-CRC therapy.

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