Risk factors for venous thromboembolism in a single pediatric intensive care unit in China.

BACKGROUND: Analyses of extensive, nationally representative databases indicate a rising prevalence of venous thromboembolism (VTE) among critically ill children. However, the majority of studies on childhood VTE have primarily concentrated on Caucasian populations in the United States and European countries. There is a lack of epidemiological studies on VTE in Chinese children. METHODS: We conducted a retrospective cohort study of data from the Pediatric Intensive Care (PIC) database. Data were obtained and extracted by using Structured Query Language (SQL) and the administrative platform pgAdmin4 for PostgreSQL. Bivariate analyses were conducted in which categorical variables were analyzed by a chi-square test and continuous variables were analyzed by a Student's t-test. Separate multivariable logistic regressions were employed to investigate the associations between VTE and sociodemographic factors as well as clinical factors. RESULTS: Our study included 12,881 pediatric patients from the PIC database, spanning the years 2010 to 2018. The incidence rate of pediatric VTE was 0.19% (24/12,881). The venous thrombotic locations were deep venous thrombosis extremities (n = 18), superior vena cava (n = 1), cerebral sinovenous (n = 1), and other deep venous thrombosis (n = 4). Univariate analysis showed that age, weight, shock, sepsis, cancer and vasopressor receipt were statistically significant risk factors for pediatric VTE (all p ≤ 0.05). After multivariable logistic regression analysis, only shock (aOR: 6.77, 95%CI: 1.33-34.73, p = 0.019) and admission for sepsis (aOR: 6.09, 95%CI: 1.76-21.09, p = 0.004) were statistically significant associated with pediatric VTE. CONCLUSIONS: In conclusion, data obtained from the Pediatric Intensive Care (PIC) database revealed a prevalence of VTE in pediatric patients of 0.19%. The most common location for venous thrombi was deep venous thrombosis (DVT) in the extremities. We identified that shock and sepsis were statistically significant factors associated with pediatric VTE.

Association of maternal blood high-mobility group box 1 levels and adverse pregnancy outcomes: A systematic review and meta-analysis.

Conflicting findings have emerged regarding the levels of high mobility group box 1 (HMGB1) in individuals experiencing adverse pregnancy outcomes. Here we conducted a meta-analysis to assess the association between maternal blood HMGB1 levels and adverse pregnancy outcomes. Utilizing databases such as PubMed, Cochrane Central Register of Controlled Trials, Web of Science, Embase and China National Knowledge Infrastructure (CNKI), a systematic literature search was conducted in January 2024. Eligible literature was screened according to inclusion and exclusion criteria. Quality assessment was evaluated using the Newcastle-Ottawa Scale (NOS). The extracted data were analyzed using Review Manager 5.4 and STATA 12.0 software. 21 observational studies with a total of 2471 participants were included in this meta-analysis. Significantly higher peripheral blood levels of HMGB1 were associated with preeclampsia (PE) (SMD=1.34; 95% CI: 0.72-1.95; P < 0.0001) and gestational diabetes mellitus (GDM) (SMD=1.20; 95% CI: 0.31-2.09; P = 0.009). Additionally, HMGB1 levels in peripheral blood were significantly elevated in patients with unexplained recurrent spontaneous abortion (URSA) than those in pregnancy controls (SMD=4.22; 95% CI: 1.64-6.80; P = 0.001) or non-pregnancy controls (SMD=3.87; 95% CI: 1.81-5.92; P = 0.0002). Interestingly, higher blood HMGB1 levels were observed in women with preterm birth (PTB), however, the results did not reach a statistical difference (SMD=0.54; 95% CI: -0.36-1.44; P = 0.24). In conclusion, overexpressed maternal blood HMGB1 levels were associated with adverse pregnancy outcomes, including PE, GDM and URSA. Further studies should be conducted to validate the efficacy of HMGB1 as a biomarker for assessing the risk of adverse pregnancy outcomes.

Association between high-mobility group box 1 levels and preeclampsia: a systematic review and meta-analysis.

PURPOSE: Previous studies had demonstrated that high-mobility group box 1 (HMGB1) levels were elevated in preeclampsia (PE). However, the conclusion remains controversial. This study aimed to investigate the association between blood and placenta HMGB1 levels and PE in pregnant women. METHODS: After a systematic literature search, eligible literature was screened according to inclusion and exclusion criteria. Data extraction and quality assessment were performed independently by two reviewers. The extracted data were analyzed using Review Manager 5.4 and STATA 12.0 software. Subgroup analysis and meta-regression analysis were conducted to find potential sources of heterogeneity. RESULTS: Twelve studies were included, with a total of 1145 participants. Compared with normal pregnancies, pregnant women with PE had significantly higher blood HMGB1 levels (SMD = 1.34, 95% CI: 0.72-1.95, p < 0.0001). Similarly, the expression of placental HMGB1 in PE was higher than that in normal controls by using Western blot (MD = 0.37, 95% CI: 0.27-0.47, p < 0.00001) or immunohistochemistry (OR = 6.36, 95% CI: 1.48-27.25, p = 0.01). In addition, the blood HMGB1 levels were positively correlated with the severity of PE, with higher blood HMGB1 levels in severe PE than those in mild PE (SMD = 3.35, 95% CI: 0.63-6.06, p = 0.02). The subgroup analysis indicated a close association of blood HMGB1 with PE in the Asian group, but not in the European group. CONCLUSION: Both blood and placental HMGB1 levels in patients with PE were significantly elevated, and higher blood HMGB1 levels indicated a more serious disease condition, suggesting that higher levels of HMGB1 were associated with the risk of PE.

Raptor mediates the selective inhibitory effect of cardamonin on RRAGC-mutant B cell lymphoma.

BACKGROUND: mTORC1 (mechanistic target of rapamycin complex 1) is associated with lymphoma progression. Oncogenic RRAGC (Rag guanosine triphosphatase C) mutations identified in patients with follicular lymphoma facilitate the interaction between Raptor (regulatory protein associated with mTOR) and Rag GTPase. It promotes the activation of mTORC1 and accelerates lymphomagenesis. Cardamonin inhibits mTORC1 by decreasing the protein level of Raptor. In the present study, we investigated the inhibitory effect and possible mechanism of action of cardamonin in RRAGC-mutant lymphoma. This could provide a precise targeted therapy for lymphoma with RRAGC mutations. METHODS: Cell viability was measured using a cell counting kit-8 (CCK-8) assay. Protein expression and phosphorylation levels were determined using western blotting. The interactions of mTOR and Raptor with RagC were determined by co-immunoprecipitation. Cells overexpressing RagC wild-type (RagCWT) and RagC Thr90Asn (RagCT90N) were generated by lentiviral infection. Raptor knockdown was performed by lentivirus-mediated shRNA transduction. The in vivo anti-tumour effect of cardamonin was assessed in a xenograft model. RESULTS: Cardamonin disrupted mTOR complex interactions by decreasing Raptor protein levels. RagCT90N overexpression via lentiviral infection increased cell proliferation and mTORC1 activation. The viability and tumour growth rate of RagCT90N-mutant cells were more sensitive to cardamonin treatment than those of normal and RagCWT cells. Cardamonin also exhibited a stronger inhibitory effect on the phosphorylation of mTOR and p70 S6 kinase 1 in RagCT90N-mutant cells. Raptor knockdown abolishes the inhibitory effects of cardamonin on mTOR. An in vivo xenograft model demonstrated that the RagCT90N-mutant showed significantly higher sensitivity to cardamonin treatment. CONCLUSIONS: Cardamonin exerts selective therapeutic effects on RagCT90N-mutant cells. Cardamonin can serve as a drug for individualised therapy for follicular lymphoma with RRAGC mutations.

Raptor couples mTORC1 and ERK1/2 inhibition by cardamonin with oxidative stress induction in ovarian cancer cells.

Background: A balance on nutrient supply and redox homeostasis is required for cell survival, and increased antioxidant capacity of cancer cells may lead to chemotherapy failure. Objective: To investigate the mechanism of anti-proliferation of cardamonin by inducing oxidative stress in ovarian cancer cells. Methods: After 24 h of drug treatment, CCK8 kit and wound healing test were used to detect cell viability and migration ability, respectively, and the ROS levels were detected by flow cytometry. The differential protein expression after cardamonin administration was analyzed by proteomics, and the protein level was detected by Western blotting. Results: Cardamonin inhibited the cell growth, which was related to ROS accumulation. Proteomic analysis suggested that MAPK pathway might be involved in cardamonin-induced oxidative stress. Western blotting showed that cardamonin decreased Raptor expression and the activity of mTORC1 and ERK1/2. Same results were observed in Raptor KO cells. Notably, in Raptor KO cells, the effect of cardamonin was weakened. Conclusion: Raptor mediated the function of cardamonin on cellular redox homeostasis and cell proliferation through mTORC1 and ERK1/2 pathways.

Baicalin suppresses the migration and invasion of breast cancer cells via the TGF-ß/lncRNA-MALAT1/miR-200c signaling pathway.

Metastasis is the major cause of death and failure of cancer chemotherapy in patients with breast cancer (BC). Activation of TGF-ß/lncRNA-MALAT1/miR-200c has been reported to play an essential role during the metastasis of BC cells. The present study aimed to validate the suppression of BC-cell migration and invasion by baicalin and explore its regulatory effects on the TGF-ß/lncRNA-MALAT1/miR-200c signaling pathway. We found that baicalin treatment inhibited cell viability and migration and invasion. Mechanistically, baicalin treatment significantly downregulated the expression of TGF-ß, ZEB1, and N-cadherin and upregulated E-cadherin on both mRNA and protein levels. Additionally, baicalin treatment significantly downregulated the expression of lncRNA-MALAT1 and upregulated that of miR-200c. Collectively, baicalin significantly suppresses cell viability, migration, and invasion of BC cells possibly by regulating the TGF-ß/lncRNA-MALAT1/miR-200c pathway.

Cardamonin suppresses pro-tumor function of macrophages by decreasing M2 polarization on ovarian cancer cells via mTOR inhibition.

Ovarian cancer is the most fatal tumor characterized by an abundance of tumor-associated macrophage (TAM) infiltrations in women. Functional TAMs, which mainly present M2-like phenotypes and perform key functions on tumor progress, have been considered an attractive target for ovarian cancer therapy. Cardamonin showed an excellent antitumor activity in multiple tumor cells. This study aimed to investigate the role of cardamonin on TAMs. With the conditioned medium of ovarian cancer cells, macrophages were induced to TAMs and, accordingly, promoted the proliferation, migration, and invasion of ovarian cancer cells. Cardamonin suppressed alternatively activated (M2) polarization of TAMs and downregulated TAM-secreted tumorigenic factors, thereby hindering the pro-tumor function of TAMs on ovarian cancer cells. Moreover, cardamonin inhibited tumor growth in xenograft nude mice and lowered the expression of CD163 and CD206. Mechanistically, cardamonin inhibited the phosphorylation of mammalian target of rapamycin (mTOR) and signal transducer and activator of transcription 3 (STAT3), resulting in the suppression of M2 polarization. Furthermore, STAT3 is tightly related with mTOR activity. Altogether, these findings implied that cardamonin suppresses the pro-tumor function of TAMs by decreasing M2 polarization via mTOR inhibition, and cardamonin may be a potential therapeutic agent for ovarian cancer.

Microelectronic structure changes electron utilization: Core-shell structure catalysts with electron library and quantum dots for photocatalytic hydrogen production.

Photocatalysis is facing huge challenges especially the separation and efficient utilization of photocarriers. Herein, we report that a ternary hollow core-shell photocatalyst is synthesized by template and self-assembled method. The experimental results show that the electron separation efficiency and utilization efficiency are significantly improved, not only because the ternary hollow core-shell structure spatially separates the oxidation area MnOx from the reduction area Co-MOF, but also because lots of emergent electrons are stored in Co-MOF as an electronic library, contributing to the formation of surface polarization to support the requirement call from the CoP quantum dots (QDs) as active-sites. It's the first report that the effectively separated electron-rich and electron-poor microelectronic states of the tunable Co-MOF promotes electron utilization by affecting the storage capacity of the electron library promoting photocatalytic hydrogen production. The tests show that Mn@Cd-CoP QDs/MCN (35.31 mmol/h/g), Mn@Cd-CoP QDs/BCN (23.69 mmol/h/g) and Mn@Cd-CoP QDs (11.08 mmol/h/g) have the better hydrogen production performances, which is about 38 times, 26 times and 12 times higher than CdS (0.9244 mmol/h/g), respectively. The pioneering exploration about the ternary hollow core-shell structure bonded with MOFs materials with abundant CoP QDs will open up a new perspective to design high-performance for solar-chemical energy conversion.

Cardamonin inhibits the expression of P-glycoprotein and enhances the anti-proliferation of paclitaxel on SKOV3-Taxol cells.

Paclitaxel is widely used in the first-line treatment of ovarian cancer. Nevertheless, the development of acquired resistance to paclitaxel is a major obstacle for the therapy in clinic. Cardamonin is a novel anticancer chalcone which exhibits a wide range of pharmacological activities. However, the effect of cardamonin on paclitaxel-resistant ovarian cancer cells and its underlying molecular mechanisms are unknown. Here, we revealed whether cardamonin had a resensitivity for paclitaxel and furtherly explored the underlying mechanisms on SKOV3-Taxol cells. Our results showed that cardamonin combined with paclitaxel had a synergistic effect of anti-proliferation in SKOV3-Taxol cells, and CI was less than one. Cells apoptosis and G2/M phase arrest were enhanced by cardamonin with paclitaxel in a concentration-dependent way on SKOV3-Taxol cells (P < 0.05). Cardamonin significantly increased drug accumulation in SKOV3-Taxol cells (P < 0.05). Similar to verapamil, cardamonin decreased MDR1 mRNA and P-gp expression (P < 0.05). Cardamonin restrained NF-κB activation in SKOV3-Taxol cells (P < 0.05). Inhibitory effect of P-gp and NF-κB p65 (nuclear protein) expression was enhanced by cardamonin combined with PDTC, a NF-κB inhibitor. Cardamonin significantly inhibited the upregulation of NF-κB p65 (nuclear protein) and P-gp expression induced by TNF-α (P < 0.05). Taken together, cardamonin enhanced the effect of paclitaxel on inhibiting cell proliferation, inducing apoptosis and G2/M phase arrest, and then strengthened the cytotoxic effect of paclitaxel in SKOV3-Taxol cells. The mechanism might be involved in inhibition of P-gp efflux pump, reducing MDR1 mRNA and P-gp expression by cardamonin via suppression of NF-κB activation in SKOV3-Taxol cells.

Cardamonin inhibits cell proliferation by caspase-mediated cleavage of Raptor.

The antiproliferative effect of cardamonin on mTORC1 is related with downregulation of Raptor. We investigated the mechanism that cardamonin decreases Raptor expression through caspase-mediated protein degradation. SKOV3 cells and HeLa cells were pretreated with caspase inhibitor z-VAD-fmk for 30 min and then exposed to different doses of cardamonin and cisplatin, respectively. We analyzed the gene expression of caspases based on TCGA and GTEx gene expression data in serous cystadenocarcinoma and normal tissues, monitored caspase activity by caspase colorimetric assay kit, detected expression of mTORC1-associated proteins and apoptosis-associated proteins by western blotting, and finally detected cell viability by methyl thiazolyl tetrazolium (MTT) assay. A different expression of caspases except caspase-1 was found between serous cystadenocarcinoma and normal tissues. Raptor was cleaved when caspases were activated by cisplatin and caspase-6/caspase-8 was activated by cardamonin in SKOV3 cells. We further used a monoclonal antibody recognizing the N-terminal part of Raptor to find that Raptor was cleaved into a smaller fragment of about 70 kDa by cardamonin and was rescued by z-VAD-fmk treatment. As a result of Raptor cleavage, mTORC1 activity was decreased and cell viability was inhibited, while cell apoptosis was induced in SKOV3 cells. Notably, similar results are only observed in HeLa cells with a high dose of cardamonin. We concluded that caspase-mediated cleavage of Raptor might be an important mechanism in that cardamonin regulated Raptor and mTORC1 activity.

High PRAS40 mRNA expression and its role in prognosis of clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is one of the most common type of kidney malignancy. The proline-rich Akt substrate of 40 kDa (PRAS40) plays an important role in tumor growth. The present study aimed to analysis the prognostic value of PRAS40 mRNA expression in ccRCC. METHODS: We analyzed the PRAS40 mRNA expression using the data from TCGA-KIRC cohort. A receiver operating characteristic (ROC) curve was performed to assessed the diagnostic value of PRAS40 mRNA expression in ccRCC. Chi-square test was used to analyzed the correlation between clinical characteristics and PRAS40 mRNA expression. Kaplan-Meier analysis and Cox analysis were performed to determine the prognostic value of PRAS40 mRNA expression in ccRCC. Gene set enrichment analysis (GSEA) was conducted using TCGA database. RESULTS: Our results revealed that PRAS40 mRNA expression was higher in ccRCC tissues than in normal tissues. PRAS40 presented a moderate diagnostic value in ccRCC. High PRAS40 mRNA expression was correlated with histological grade, clinical stage, T classification, distant metastasis and vital status of ccRCC. High PRAS40 mRNA expression was associated with poor overall survival. Furthermore, Multivariate analysis revealed that PRAS40 was an independent risk factor for ccRCC patients. Myc targets, DNA repair, oxidative phosphorylation, glycolysis, adipogenesis, p53 pathway, reactive oxygen species pathway, myogenesis were differentially enriched in the phenotype that positively correlated with PRAS40. CONCLUSIONS: In conclusion, our results suggest that PRAS40 was a promising diagnostic and prognostic biomarker for ccRCC.

DAP1 negatively regulates autophagy induced by cardamonin in SKOV3 cells.

Autophagy is closely related to the formation and development of multiple human tumors including ovarian cancer. As a major regulator of this process, the role of mTOR (mammalian target of rapamycin) has been well proven. Cardamonin, a kind of flavonoid from plants, has effects on induction of autophagy and thus antiproliferation of cancer cells. However, the detailed mechanism remains unclear. DAP1 (death-associated protein 1) is a proline-rich protein, which is involved in the regulation of cellular growth and programmed cell death including autophagy and apoptosis. The aim of this study was to investigate whether DAP1 is involved in proliferation inhibition and autophagy induced by cardamonin in tumor cells. Using online bioinformatics tools, we found that DAP1 expression is closely related to the survival of patients with ovarian cancer. Our study showed that autophagy induced by cardamonin was associated with mTOR inhibition, and DAP1 was involved in this process. Silence of DAP1 decreased cell proliferation but enhanced the antiproliferative effect of cardamonin in SKOV3 cells. The level of autophagy was elevated by DAP1 silencing in SKOV3 cells. Notably, cardamonin showed higher autophagy flux in the DAP1 small interfering RNA group. Taken together, our results implied that DAP1 negatively regulates autophagy induced by cardamonin, and it may be a potential target for ovarian cancer therapy.

Anti­proliferative effect of cardamonin on mTOR inhibitor­resistant cancer cells.

A number of mammalian target of rapamycin (mTOR) inhibitors have been approved for the treatment of certain types of cancer or are currently undergoing clinical trials. However, mTOR targeted therapy exerts selective pressure on tumour cells, which leads to the preferential growth of resistant subpopulations. There are two classes of mTOR inhibitors: i) The rapalogs, such as rapamycin, which bind to the 12­kDa FK506­binding protein/rapamycin­binding domain of mTOR; and ii) the ATP­competitive inhibitors, such as AZD8055, which block the mTOR kinase domain. Cardamonin inhibits mTOR by decreasing the expression of regulatory­associated protein of mTOR (Raptor), a mechanism of action which differs from the currently available mTOR inhibitors. The present study investigated the inhibitory effects of cardamonin on mTOR inhibitor­resistant cancer cells. HeLa cervical cancer cells and MCF­7 breast cancer cells were exposed to high concentrations of mTOR inhibitors, until resistant clones emerged. Cytotoxicity was measured using the MTT and colony forming assays. The inhibitory effect of cardamonin on mTOR signalling was assessed by western blotting. The resistant cells were less sensitive to mTOR inhibitors compared with the parental cells. Consistent with the anti­proliferation effect, rapamycin and AZD8055 had no effect on the phosphorylation of rapamycin­sensitive sites on ribosomal protein S6 kinase B1 (S6K1) and AZD8055­sensitive sites on protein kinase B and eukaryotic translation initiation factor 4E binding protein 1 (Thr 37/46), respectively, in rapamycin­ and AZD8055­resistant cells. Cardamonin inhibited cell proliferation and decreased the phosphorylation of mTOR and S6K1, as well as the protein level of raptor, in the mTOR inhibitor­resistant cells. Therefore, cardamonin may serve as a therapeutic agent for patients with cervical and breast cancer resistant to mTOR inhibitors.

Glycolysis inhibition via mTOR suppression is a key step in cardamonin-induced autophagy in SKOV3 cells.

BACKGROUND: Autophagy occurs in cells that undergoing nutrient deprivation. Glycolysis rapidly supplies energy for the proliferation of cancer cells. Cardamonin inhibits proliferation and enhances autophagy by mTORC1 suppression in ovarian cancer cells. Here, we investigate the relationship between cardamonin-triggered autophagy and glycolysis inhibition via mTORC1 suppression. METHODS: Treated with indicated compounds, ATP content and the activity of hexokinase (HK) and lactate dehydrogenase (LDH) were analyzed by the assay kits. Autophagy was detected by monodansylcadaverin (MDC) staining. The relationship between cardamonin-triggered autophagy and glycolysis inhibition via mTORC1 suppression was analyzed by Western blot. RESULTS: We found that cardamonin inhibited the lactate secretion, ATP production, and the activity of HK and LDH. The results demonstrated that cardamonin enhanced autophagy in SKOV3 cells, as indicated by acidic compartments accumulation, microtubule-associated protein 1 Light Chain 3-II (LC3-II) and lysosome associated membrane protein 1 up-regulation. Our results showed that the activation of mTORC1 signaling and the expression HK2 were reduced by cardamonin; whereas the phosphorylation of AMPK (AMP-activated protein kinase) was increased. We also confirmed that the AMPK inhibitor, Compound C, reversed cardamonin-induced upregulation of LC3-II. CONCLUSION: These results suggest that cardamonin-induced autophagy is associated with inhibition on glycolysis by down-regulating the activity of mTORC1 in ovarian cancer cells.

Anti-inflammatory Effects of Cardamonin in Ovarian Cancer Cells Are Mediated via mTOR Suppression.

Cardamonin exhibits a variety of pharmacological activities including anti-inflammatory and antitumor, which are correlated with the inhibition of nuclear factor-kappaB and the mammalian target of rapamycin, respectively. However, whether the anti-inflammatory effects of cardamonin are mediated by the mammalian target of rapamycin remains unknown. In this study, ovarian cancer SKOV3 cells were cultured with lipopolysaccharide to induce inflammation, and the inhibitory effects and underlying molecular mechanisms of cardamonin were investigated using specific inhibitors of the mammalian target of rapamycin and the nuclear factor-kappaB pathway (rapamycin and pyrrolidine dithiocarbamate, respectively). Our results indicated that cardamonin inhibited the viability of normal and lipopolysaccharide-pretreated SKOV3 cells in a concentration-dependent manner. In accordance with rapamycin, the activation of the mammalian target of rapamycin and its downstream target, ribosomal protein S6 kinase 1, was inhibited by cardamonin, while pyrrolidine dithiocarbamate substantially blocked nuclear factor-kappaB activation and mildly inhibited the phosphorylation of the mammalian target of rapamycin and ribosomal protein S6 kinase 1. Pretreated with pyrrolidine dithiocarbamate, the effect of cardamonin on the mammalian target of rapamycin signalling was not affected, but the expression of inflammatory factors was further reduced. In cells pretreated with rapamycin, the inhibitory effects of cardamonin were completely suppressed with regards to the phosphorylation of the mammalian target of rapamycin, ribosomal protein S6 kinase 1, TNF-α, and interleukin-6, and nuclear factor-kappaB p65 protein expression was decreased. In conclusion, our findings indicate that the anti-inflammatory effects of cardamonin are correlated with mammalian target of rapamycin inhibition.

Raptor mediates the antiproliferation of cardamonin by mTORC1 inhibition in SKOV3 cells.

PURPOSE: Cardamonin inhibits the proliferation of SKOV3 cells by suppressing the mammalian target of rapamycin complex 1 (mTORC1). However, the mechanism of cardamonin on mTORC1 inhibition has not been well demonstrated. The regulatory-associated protein of TOR (Raptor) is an essential component of mTORC1. Here, we investigated the role of Raptor in the mTORC1 inhibition effect of cardamonin in SKOV3 cells. METHODS: The expression of Raptor was knockdown by small interfering RNA (siRNA). The expressions of specific binding proteins of mTORC1 were analyzed by Western blotting, and the cell proliferation was detected by methyl thiazolyl tetrazolium (MTT) assay. RESULTS: Rapamycin, AZD8055, and cardamonin inhibited the activity of mammalian target of rapamycin (mTOR). Different from rapamycin and AZD8055, cardamonin suppressed the phosphorylation and protein expression of Raptor. Transfected with Raptor siRNA, the mTOR activation and proliferation of SKOV3 cells were decreased, and these effects were strengthened by cardamonin in Raptor siRNA SKOV3 cells. Cardamonin interfered with the lysosomal colocalization of mTOR with lysosomal associated membrane protein 2 (LAMP2), which was also hindered by Raptor siRNA. Furthermore, cardamonin strengthened the inhibitory effect on the lysosomal localization of mTOR in Raptor siRNA cells. CONCLUSION: Our results suggested that Raptor mainly mediated the inhibition of cardamonin on mTORC1 in SKOV3 cells.