miR-155 Regulates GSK-3β Expression and Affects Cartilage Matrix Degradation in the Pathogenesis of Osteoarthritis

2019 ◽  
Vol 9 (8) ◽  
pp. 1133-1139
Author(s):  
Xianjun Chen ◽  
Lin Shi ◽  
Qingjiang Pang ◽  
Xiao Yu ◽  
Ji Yang
Keyword(s):  
Caspase 3 ◽  
Sham Group ◽  
Cartilage Matrix ◽  
Cartilage Tissue ◽  
Control Group ◽  
Traumatic Amputation ◽  
Normal Cartilage ◽  
Pathway Activity ◽  
Col2a1 Expression ◽  
Gsk 3Β

Abnormal expression of GSK-3β is associated with the pathogenesis of osteoarthritis (OA). The miR-155 expression in cartilage tissue of OA patients was significantly elevated. A relationship between miR-155 and GSK-3β is predicted by the software. This study investigated whether miR155 regulates GSK-3β expression, affects Wnt/β-catenin pathway activity in OA. The cartilage tissues of OA patients and normal cartilage tissues after traumatic amputation were collected. The OA rat model was established and divided into OA + antagomir control group, OA + miR-155 antagomir group followed by analysis of expression of miR-155, GSK-3β, β-catenin and COL2A1 by qRT-PCR, Hyp content by ELISA, caspase-3 activity, and GSK-3β, β-catenin, COL2A1 expression by western blot. Compared to control group, the expression of miR-155 and -catenin in cartilage tissue of OA patients was significantly elevated and GSK-3β level was reduced. There was a targeted regulation relationship between miR-155 and GSK-3β. OA group had significantly higher miR-155 and β-catenin expression and lower GSK-3 and COL2A1 level in the cartilage than sham group. Compared with OA + antagomir control group, miR-155 and β-catenin expression and caspase-3 activity in OA + miR-155 antagomir group were significantly decreased, with increased expression of GSK3β and COL2A1 and reduced Hyp content. Increased miR-155 expression can decrease GSK-3β expression, enhance Wnt/β-catenin pathway activity, promote the degradation and destruction of cartilage matrix and inhibit miR-155 expression, thus ameliorating the development and progress of OA.

Celecoxib Attenuates Cartilage Matrix Damage in Arthritis Rats by Inhibiting NF-κ B

2020 ◽  
Vol 10 (4) ◽  
pp. 531-537
Author(s):  
Lukuan Du ◽  
Zhenghui Jiang ◽  
Zhaohui Wang ◽  
Liming Wang
Keyword(s):  
Caspase 3 ◽  
Sham Group ◽  
Culture Supernatant ◽  
Cartilage Tissue ◽  
Chondrocyte Apoptosis ◽  
Control Group ◽  
Therapeutic Effects ◽  
Protein Expressions ◽  
Col2a1 Expression ◽  
Matrix Damage

Objective: Celecoxib selectively inhibits the activity of COX-2 and the production of prostaglandin (PG), and plays a therapeutic role in treating osteoarthritis (OA). NF-κB signaling and IL-1α and TNFα are involved in OA pathogenesis. This study explored whether Celecoxib might exert therapeutic effects on OA through regulating NF-κB signaling and IL-1β and TNF release in OA rat model. Method : The contents of MMP-13, Hyp, IL-1β and TNFα in synovial fluid were detected by ELISA. The protein expressions of NF-κ B p-p65, COL2A1 and the activity of caspase-3 were detected. OA model rats were separated into OA group and OA+ Celecoxib group followed by analysis of MMP-13, Hyp, IL-1β and TNF level in articular fluid by ELISA and p-p65 and COL2A1 level and caspase-3 activity by western blot. Rat cartilage tissue was cultured and divided into control group, LPS group and LPS+ Celecoxib group followed by analysis of expressions of p-p65 and COL2A1 in cartilage tissue, IL-1 and TNF content in culture supernatant, and chondrocyte apoptosis. Results: Compared with Sham group, p-p65 expression and caspase-3 activity in cartilage tissue of OA rats was increased and COL2A1 level was reduced. Meanwhile the expression of MMP-13, Hyp, IL-1β and TNF in articular fluid of OA rats was increased. Compared to OA group, p-p65 expression and caspase-3 activity was decreased and COL2A1 expression was increased in OA+ Celecoxib treatment group along with decreased MMP-13, Hyp, IL-1β and TNF level in articular fluid. p-p65 expression and caspase-3 activity in LPS group was increased and COL2A1 expression was decreased with increased IL-beta; and TNF content. Compared to LPS group, p-p65 expression and caspase-3 activity was decreased and COL2A1 expression was increased in LPS+ Celecoxib group with decreased content of IL-1β and TNFα. Conclusion: Celecoxib can protect cartilage in OA by inhibiting NF-κB activation and IL-1β and TNF release, and decreasing cell apoptosis in inflammatory environment.

miR-211 Reduces the Degradation of Articular Cartilage Matrix by Targeting Matrix Metalloproteninase 9

2019 ◽  
Vol 9 (9) ◽  
pp. 1292-1297
Author(s):  
Yumei Tian ◽  
Jian Wang
Keyword(s):  
Cartilage Damage ◽  
Cartilage Matrix ◽  
Cartilage Tissue ◽  
Control Group ◽  
Matrix Degradation ◽  
Mankin Score ◽  
Joint Cavity ◽  
Mmp9 Expression ◽  
Col2a1 Expression ◽  
And Cartilage

Matrix metalloproteninase 9 (MMP9) promotes osteoarthritis (OA) cartilage matrix degradation. Abnormal miR-211 expression is associated with OA. Bioinformatics analysis showed a targeted relationship between miR-211 and MMP9 mRNA 3′-UTR. Our study intends to evaluate miR-211’s role in the destruction of chondrocyte matrix in OA model rats. The OA model rats were divided into OA group, OA group+agomir-NC group, OA group+agomir-211 group, followed by analysis of the arthritis Mankin score, Hyp and IL-1β content by ELISA, MMP-9 and COL2A1 expression by western blot and miR-211 level by qRT-PCR. The cartilage tissues were divided into control group, IL-1β+ agomir-NC group, IL-1β+ agomir-211 group, and the expression of MMP-9 and COL2A1 in chondrocytes were detected. Compared with Sham group, IL-1β and Hyp levels in the joint cavity fluid of the OA group were significantly increased and miR-211 expression was significantly decreased with increased MMP9 expression and decreased COL2A1 expression. Injection of agomir-211 into the joint cavity of OA rats significantly reduced MMP9 expression in cartilage tissue, decreased Hyp content in the joint cavity fluid, increased COL2A1 expression, and decreased Mankin score and cartilage damage. IL-1β treatment significantly up-regulated MMP9 expression and decreased COL2A1 expression; miR-211 overexpression attenuated IL-1β-induced cartilage matrix degradation and cartilage destruction. miR-211 plays a role in regulating MMP9 expression and promoting OA. miR-211 overexpression inhibits MMP9 expression, reduces the degradation of cartilage matrix and increases collagen synthesis, thus ameliorating OA development.

Effect of miR-9 on Chondrocyte Apoptosis in Rats with Osteoarthritis by Regulating Notch1

2020 ◽  
Vol 10 (3) ◽  
pp. 371-378
Author(s):  
Xiao Zhong ◽  
Xiaodong Deng ◽  
Jian Luo ◽  
Ming Xiong ◽  
Wen Li ◽  
...  
Keyword(s):  
Western Blot ◽  
Caspase 3 ◽  
Notch Signaling Pathway ◽  
Cartilage Matrix ◽  
Cartilage Tissue ◽  
Chondrocyte Apoptosis ◽  
Control Group ◽  
Matrix Degradation ◽  
Qrt Pcr ◽  
Protein Expressions

Objective: Notch1 is an important receptor in Notch signaling pathway. Abnormal Notch1 expression or function is associated with the pathogenesis of OA. There is evidence that the abnormal expression of miR-9 is related to the pathogenesis of OA. Bioinformatics analysis showed that there was a targeting relationship between miR-9 and Notch1’s 3′-UTR, suggesting that there might be a mutual regulation between them. In this study, we established an OA rat model to investigate whether miR-9 plays a role in regulating Notch1 expression, affecting cartilage matrix degradation and chondrocyte apoptosis in OA. Methods: OA model rats were divided into three groups: OA group, OA + agomir group, OA + miR-9 agomir group. The content of Hyp in articular fluid was measured by ELISA, the activity of caspase-3 was detected by kit, the mRNA expressions of miR-9, COL2A1, Notch1 and Hes5 was detected by qRT-PCR, and the protein expressions of Notch1 and Hes5 in articular cartilage was detected by Western blot. Chondrocytes were separated into control group, IL-1β +miR-NC group, IL-1β +miR-9 mimic group followed by analysis of mRNA expressions of miR-9, COL2A1, Notch1 and Hes5 were detected by qRT-PCR, protein expressions of Notch1 and Hes5 by Western blot, and cell apoptosis by flow cytometry. Results: Compared with Sham group, the levels of IL-1β , Hyp, Notch1, Hes5 and Caspase-3 in the synovial fluid of rats in OA group were increased significantly, while the mRNA expressions of miR-9, COL2A1 and Notch1 and Hes5 level in cartilage tissue were decreased significantly. Intra-articular injection of miR-9 agomir could significantly reduce the content of Hyp, the mRNA expressions of Notch1 and Hes5 and the activity of caspase-3 in cartilage tissue of OA rats, increase the mRNA expressions of miR-9 and COL2A1, and decrease the protein expressions of Notch1 and Hes5. After treated with IL-1β , the expressions of Notch1 and Hes5 were increased, the mRNA expressions of miR-9 and COL2A1 were decreased, and apoptosis of chondrocyte was increased in chondrocyte. After miR-9 mimic transfection, miR-9 and COL2A1 mRNA expressions were increased, Notch1 and Hes5 expressions were decreased, and apoptosis of chondrocyte was decreased under IL-1β treatment. Conclusion: Reduced miR-9 expression upregulates Notch1 expression and promotes the pathogenesis of OA. Increased miR-9 expression can inhibit Notch1 expression, reduce cartilage matrix degradation and inhibit chondrocyte apoptosis.

Protective effect of GSK-3β/Nrf2 mediated by dimethyl fumarate in middle cerebral artery embolization reperfusion rat model

2021 ◽  
Vol 18 ◽  
Author(s):  
Yuan Li ◽  
Lan Chu ◽  
Chunfeng Liu ◽  
Zongyi Zha ◽  
Yuanlu Shu
Keyword(s):  
Oxidative Stress ◽  
Protective Effect ◽  
Sham Group ◽  
Infarct Volume ◽  
Dimethyl Fumarate ◽  
Control Group ◽  
Related Factor ◽  
Nissl Staining ◽  
Gsk 3Β ◽  
Nrf2 Expression

Aim: This study investigated the protective effect of dimethyl fumarate (DMF) in rats by mediating GSK3-β/Nrf2 using the middle cerebral artery embolization reperfusion (MCAO/R) rat model. Background: After an acute ischemic stroke (AIS), oxidative stress occurs. Dimethyl fumarate (DMF), a nuclear factor-E2-related factor 2 (Nrf2) activator, approved by the US Food and Drug Administration (FDA), was observed to regulate the Nrf2 pathway by acting as an anti-oxidative stress agent; however, whether this agent is involved in inhibiting GSK-3β remains to be established. Methods: DMF model was used to explore the effects of GSK-3β on Nrf2 expression level, Nrf2-ARE binding activity and Nrf2/ARE downstream expression level of anti-oxidant stress protein in Cerebral ischemia-reperfusion injury (CIRI). 60 rats were randomly divided into Sham group, MCAO/R group, solvent control group (DMSO group) and DMF treatment group, with 15 rats in each group. The MCAO/R, DMSO and DMF groups were considered in the MCAO/R model using the modified thread embolization method. In contrast, the Sham group was only anaesthetized and disinfected, and tissue muscle was dissected without inserting suture emboli. DMF group was gavaged with 45mg/kg per day of DMF, DMSO control group was gavaged with DMSO of equal volume, while MCAO/R group was only modeled without any intragastric treatment. The rats were treated seven days after the operation, and a neurological function Longa score was estimated. The rats were sacrificed seven days later, and the infarct volume was assessed by TTC staining. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in rat brain tissue. Nissl staining was used to observe the expression of neurons in the infarcted cortex. Western blotting (WB) was used to observe the protein expression levels of glycogen synthase kinase 3β(GSK-3β), nuclear factor E2-related factor 2 (Nrf2), downstream heme oxygenase 1 (HO1) and NADPH quinone oxidoreductase 1 (NQO1) in four groups. The expression levels of GSK-3β and Nrf2 in the four groups were observed by immunohistochemistry and immunofluorescence. Results: (1) The Longa score of the MCAO/R, DMSO and DMF groups was found to be higher compared to the Sham group, indicating successful operation. The Longa score of the DMF group was lower than that of the other three groups 4-7 days after surgery (P<0.05). (2) HE and Nissl staining showed that the DMF group had lower neuron necrosis and higher gliosis compared to the control groups. (3) TTC staining results showed that the infarct volume of the DMF group was significantly smaller than the MCAO/R and DMSO groups. (4) Protein results showed that the GSK-3β expression in the DMF group was lower than that in all groups, while the expression of Nrf2, HO1 and NQO1 was higher compared to other groups. Conclusion: DMF can reduce neurological deficits and infarct size in the MCAO/R model. The protective effect may be related to decreased GSK-3β expression and increased Nrf2 expression, which may play a role in anti-oxidative stress.

scholarly journals Apoptosis of cardiomyocytes in diabetic cardiomyopathy involves overexpression of glycogen synthase kinase-3β

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Wei Wu ◽  
Xingxing Liu ◽  
Longfei Han
Keyword(s):  
Mrna Expression ◽  
Diabetic Cardiomyopathy ◽  
Myocardial Injury ◽  
Caspase 3 ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Control Group ◽  
Glycogen Synthase Kinase 3Β ◽  
Rat Cardiomyocytes ◽  
Gsk 3Β

Abstract To evaluate the role of glycogen synthase kinase-3β (GSK-3β) in the apoptosis of cardiomyocytes in diabetic cardiomyopathy (DCM). Diabetes mellitus (DM) in rats was induced by intraperitoneal injection of 1% streptozotocin (STZ), and lithium chloride (LiCl) was used to decrease the expression of GSK-3β. Hematoxylin/eosin (HE) staining and the terminal deoxyribonucleotide transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay was conducted to evaluate the pathological injury and apoptosis of cardiomyocytes respectively. Western blot was applied to detect the protein expressions of Cleaved-caspase 3, caspase 3, Bax and Bcl-2 in rat cardiomyocytes. Real-time polymerase chain reaction (RT-PCR) was applied to detect the gene expressions of phosphoinositide 3-kinases (PI3K), Akt, and GSK-3β in rat cardiomyocytes. DM-induced cardiomyocyte injuries, which were presented as capillary basement membrane thickening, interstitial fibrosis, cardiomyocyte hypertrophy and necrosis in HE staining and increased apoptosis detected by TUNEL assay. When comparing with the control group, the mRNA expression of PI3K and Akt in DM group obviously decreased but the mRNA expression of GSK-3β obviously elevated (P < 0.05). In addition, the ratio of Cleaved-caspase 3/caspase 3 and Bax/Bcl-2 were notably increased in DM group compared with control group (P < 0.05). LiCl, as an inhibitor of GSK-3 apparently reduced the expression of GSK-3β mRNA (P < 0.05) but not the PI3K and Akt comparing with the DM group. LiCl also attenuated the myocardial injury and apoptosis induced by DM. The myocardial injury induced by DM is associated with the up-regulation of GSK-3β. LiCl inhibited the expression of GSK-3β and myocardial apoptosis in diabetic myocardium.

MiR-144-3p Regulates Lipopolysaccharide-Stimulated Chondrocyte Biological Behavior via Wingless-Related Integration Site/Beta-Catenin

2021 ◽  
Vol 11 (8) ◽  
pp. 1612-1617
Author(s):  
Nanxin Zhang ◽  
Kuangda Li ◽  
Qiong Han ◽  
Maohou Wu ◽  
Qiang Li
Keyword(s):  
Cell Proliferation ◽  
Protein Expression ◽  
Caspase 3 ◽  
Biological Behavior ◽  
Cartilage Tissue ◽  
Control Group ◽  
Beta Catenin ◽  
Activity Increase ◽  
Signaling Protein ◽  
Promote Cell Proliferation

Osteoarthritis (OA) gradually affects all joint tissues. Chondrocytes participate in osteoarthritis. However, the role and mechanism of MiR-144-3p on chondrocytes during the development of OA has not been elucidated. OA patients and normal bone and articular cartilage tissues were collected to measure MiR-144-3p level by Real-time PCR. Chondrocytes were divided into control group, LPS group (1 μg/ml lipopolysaccharide (LPS) was added to establish an osteoarthritis (OA) stimulation model, and MiR-144-3p inhibitor group which was transfected with MiR-144-3p inhibitor followed by analysis of cell proliferation by MTT, Caspase 3 activity, Wnt/β-catenin signaling protein expression by Western blot and TNF-α and IL-6 secretion by ELISA. MiR-144-3p was significantly upregulated in OA patients (P <0.05). In LPS group, MiR-144-3p was significantly upregulated, chondrocyte proliferation decreased, Caspase 3 activity increased, Wnt/β-catenin signaling protein decreased, and TNF-α and IL-6 secretion increased (P <0.05). MiR-144-3p inhibitor transfection can significantly down-regulate MiR-144-3p, promote cell proliferation, reduce Caspase 3 activity, increase Wnt/β-catenin signaling protein expression, and reduce TNF-α and IL-6 secretion (P <0.05). MiR-144-3p is upregulated in osteoarthritis cartilage tissue. Inhibition of MiR-144-3p can inhibit articular chondrocytes apoptosis under inflammatory condition, promote cell proliferation, and alleviate joint inflammation by regulating Wnt/β-catenin signaling pathway.

scholarly journals Effects of L-Carnitine on follicular reserve and Caspase-3 in transplanted mouse ovarian tissue

2019 ◽  
Author(s):  
Fatemeh Shahi Sadrabadi ◽  
Kazem Parivar ◽  
Hussein Imani ◽  
Abdolhussein Shahverdi
Keyword(s):  
Caspase 3 ◽  
Sham Group ◽  
Ischemia Reperfusion ◽  
Ovarian Tissue ◽  
Control Group ◽  
Ovarian Tissue Transplantation ◽  
Study Results ◽  
Significant Difference ◽  
Follicular Reserve ◽  
One Way Anova

Introdution: One of the major challengs in ovarian tissue transplantation is overcomeing ischemia/ reperfusion injuries. During ischemia–reperfusion processes, oxygen free radicals constitute the most important component that induces damage of the grafted tissues. The aim of this study was to investigate the effect of L-Carnitine (LC) as an antioxidant on heterotopic transplantation of mouse ovarian tissue. Methods: In this laboratory experimental study, 5- week old female NMRI mice were divided into four groups: control, transplanted without administration (autograft), sham group (autograft+ saline) and LC group (autograft+ L- carnitine). Left ovarian tissues were transplanted into the Gluteal muscle for 3 weeks. After this time, ovarian tissues from all groups were removed and fixed in formalin for histological studies. Furthermore, rate of Caspase- 3 was assessed by immunohistochemistry test. Lipid peroxidation was assessed by measuring  malondialdehyde (MDA). One-way ANOVA and Tudey test was used to analyze the data using the spss 16 software. Significance was defined as P≤0.0. Results: The study results indicated that total follicular count in transplantedwithout administration and sham groups was significantly lower than the control group (p<0.05), but there was no significant difference between the control and LC groups. In addition, the rate of caspase-3 was decreased in the LC group, but no significant difference existed between all groups (p<0.05). A significant reduction in the concentration of MDA was observed in the LC group than that in the other transplanted groups (p<0.05). Conclusion: In this study, LC could improve the ovarian reserve to some extent, but its effect was not significant.

scholarly journals Does Nimodipine, a Selective Calcium Channel Blocker, Impair Chondrocyte Proliferation or Damage Extracellular Matrix Structures?

2019 ◽  
Vol 20 (6) ◽  
pp. 517-524
Author(s):  
Necati Kaplan ◽  
Ibrahim Yilmaz ◽  
Numan Karaarslan ◽  
Yasin E. Kaya ◽  
Duygu Y. Sirin ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Active Ingredient ◽  
Cellular Proliferation ◽  
Hypoxia Inducible Factor ◽  
Type Ii Collagen ◽  
Cartilage Tissue ◽  
Control Group ◽  
Chondrocyte Proliferation ◽  
Hypoxia Inducible Factor 1 ◽  
Col2a1 Expression

Background: The study aimed to investigate the effects of the active ingredient, nimodipine, on chondrocyte proliferation and extracellular matrix (ECM) structures in cartilage tissue cells. Methods: Chondrocyte cultures were prepared from tissues resected via surgical operations. Nimodipine was then applied to these cultures and molecular analysis was performed. The data obtained were statistically calculated. Results: Both, the results of the (3-(4,5 dimethylthiazol2-yl)-2,5-diphenyltetrazolium (MTT) assay and the fluorescence microscope analysis [a membrane permeability test carried out with acridine orange/ propidium iodide staining (AO/PI)] confirmed that the active ingredient, nimodipine, negatively affects the cell cultures. Conclusion: Nimodipine was reported to suppress cellular proliferation; chondroadherin (CHAD) and hypoxia-inducible factor-1 alpha (HIF-1α) expression thus decreased by 2.4 and 1.7 times, respectively, at 24 hrs when compared to the control group (p < 0.05). Furthermore, type II collagen (COL2A1) expression was not detected (p<0.05). The risk that a drug prescribed by a clinician in an innocuous manner to treat a patient by relieving the symptoms of a disease may affect the proliferation, differentiation, and viability of other cells and/or tissues at the molecular level, beyond its known side effects or adverse events, should not be forgotten.

Effect of LncRNA Cancer Upregulated Drug Resistant (CUDR) on Osteoarthritis Chondrocyte Proliferation and Apoptosis by Regulating NF-κB Signaling Pathway

2020 ◽  
Vol 10 (12) ◽  
pp. 1871-1876
Author(s):  
Shaohua Liu ◽  
Guanming Zhou ◽  
Xicong Chen ◽  
Huiliang Zeng ◽  
Jian Cai
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Articular Chondrocytes ◽  
The Body ◽  
Cartilage Tissue ◽  
Control Group ◽  
Promote Cell Proliferation ◽  
Proliferation And Apoptosis ◽  
Oa Chondrocytes

Osteoarthritis (OA) is a common and frequently-occurring disorder in orthopedics. LncRNA CUDR involves in several physiological and pathological activities of the body. However, the role and mechanism of LncRNA CUDR in OA has not been elucidated. Cartilage tissue from OA patients and normal bone and joints were collected to detect LncRNA CUDR level by Real-time PCR. Chondrocytes from OA patients were isolated and divided into control group, LncRNA CUDR siRNA group, and LncRNA CUDR group followed by analysis of cell proliferation by MTT assay, Caspase 3 activity, NF-κB expression by Western blot, secretion of TNF-α and IL-6 by ELISA. LncRNA CUDR was significantly higher in OA patients than controls (P <0.05). LncRNA CUDR siRNA transfection into OA chondrocytes can significantly down-regulate LncRNA CUDR expression, promote cell proliferation, and reduce Caspase 3 activity, NF-κB level, as well as TNF-α and IL-6 secretion (P <0.05). Transfection of pcDNALncRNA CUDR plasmid into OA chondrocytes could up-regulate the expression of LncRNA CUDR and significantly reverse the above changes (P <0.05). LncRNA CUDR expression is increased in OA patients. Down-regulating LncRNA CUDR can inhibit the apoptosis and promote proliferation of articular chondrocytes and inhibit arthritis by down-regulating the NF-κB signaling pathway

Effects of Papaya Leaf Extract (Carica papaya L.) on Cellular Proliferation and Apoptosis in Cervical Cancer Mice Model

2019 ◽  
Vol 17 (5) ◽  
pp. 265-275
Author(s):  
Y. Peristiowati ◽  
Y. Puspitasari ◽  
Indasah
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Hela Cells ◽  
Leaf Extract ◽  
Caspase 3 ◽  
Methanol Extract ◽  
Negative Control ◽  
Proliferation Index ◽  
Control Group ◽  
P53 Expression

This study is aimed at analyzing the anticancer properties of papaya leaf extract, specifically the inhibition of cell proliferation and apoptotic induction through nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and p53 pathways. Twenty-five mice (Mus musculus), aged 2 months and weighing 20–30 g, was injected with 0.5 mg dexamethasone for 7 days. The mice were then injected intracutaneously with 1 ml of HeLa cells (8 × 106 HeLa cells/microliter). The mice were divided into five groups (5 each): negative control (P1) (5% CMC-Na, sodium carboxymethyl cellulose), treatment II (225 mg/kg BW (body weight) papaya leaves methanol extract), treatment III (450 mg/kg BW), treatment IV (750 mg/kg BW), and treatment PV (2 mg alcohol anticancer drug). Papaya leaf extract treatments were applied for 2 weeks. Then, the tumor tissue was isolated for hematoxylin and eosin staining. Immunohistochemical imaging was used to detect Ki-67, caspase-3, NF-κB, and p53 expression. Further analysis was undertaken using the ImmunoRatio software program. The results indicated that administration of papaya leaf methanol extract significantly increased the expression of NF-κB and p53 at a dose of 450 mg/kg BW. Our results also showed that the mice treated with 450 mg of papaya leaf extract per kg of BW (P3) had the largest increase of caspase-3 expression compared to the negative control group. Papaya leaf ethanol extract decreased the cancer cell proliferation index and increased apoptosis of cancer cells in animal models of cervical cancer; it may also work to increase NF-kB expression and expression of the p53 gene.

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