Hedyotis diffusa Willd. Suppresses Hepatocellular Carcinoma via Downregulating AKT/mTOR Pathways

Objective. Hedyotis diffusa Willd. (HDW) is a famous Chinese herbal medicine, traditionally used to treat cancer in China. Currently, the clinically used drugs for the treatment of hepatocellular carcinoma (HCC) still have poor efficacy and have many side effects. HDW has fewer side effects after taking it, so this study explores the inhibitory effect of HDW on HCC, which may become a promising drug for the treatment of HCC. Methods. HCC cell lines such as SMMC-7721, SK-hep1, and Hep-G2 were treated with Hedyotis diffusa Willd. (HDW), after which migration was detected via transwell, while the proliferation of these cells was detected via MTT, CCK-8, and colony formation assays. Furthermore, protein levels were evaluated by western blotting, and Hep-G2 cells were implanted in nude mice to establish a xenograft model to evaluate the antitumor effect of the drug. Results. HDW exhibited the ability to inhibit the proliferation and migration of HCC cells. And its anticancer mechanism in hepatocellular carcinoma may be via AKT/mTOR pathway. Moreover, the drug use of HDW in the mouse model system has achieved a good effect. Importantly, it did not cause significant weight loss or hepatorenal toxicity. Conclusion. HDW can suppress the activation of the AKT/mTOR pathway in HCC cells, which may bring new light for the treatment of this kind of malignant tumor, but its exact mechanism still needs to be further explored.

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Lidocaine has antitumor effect on hepatocellular carcinoma via the circ_DYNC1H1/miR-520a-3p/USP14 axis

Open Life Sciences ◽

10.1515/biol-2021-0072 ◽

2021 ◽

Vol 16 (1) ◽

pp. 766-780

Author(s):

Hua Liu ◽

Jing Cheng ◽

Heng Xu ◽

Zhenzhen Wan

Keyword(s):

Hepatocellular Carcinoma ◽

Xenograft Model ◽

Circular Rna ◽

Inhibitory Effect ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Chain Gene ◽

Protein Levels ◽

Hcc Cells

Abstract Lidocaine can inhibit the malignant development of various human cancers. Circular RNA (circRNA) dynein 1 heavy chain gene (circ_DYNC1H1) acted as a pro-cancer molecule in hepatocellular carcinoma (HCC). This study aimed to explore whether the function of lidocaine was related to the oncogenic circ_DYNC1H1 in HCC. Colony formation assay and 3-(4,5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay were used for proliferation detection. Cell apoptosis was assessed by flow cytometry, and migration or invasion was determined by the transwell assay. The levels of circ_DYNC1H1, microRNA-520a-3p (miR-520a-3p), and ubiquitin-specific protease 14 (USP14) were examined using the quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Protein levels were measured using western blot. The binding between miR-520a-3p and circ_DYNC1H1 or USP14 was confirmed by the dual-luciferase reporter assay. In vivo assay was conducted by a xenograft model in mice. Lidocaine reduced proliferation, migration, and invasion but promoted apoptosis in HCC cells. The circ_DYNC1H1 expression was downregulated in lidocaine-treated HCC cells. The inhibitory effect of lidocaine on HCC progression was weakened after circ_DYNC1H1 overexpression. miR-520a-3p was a target of circ_DYNC1H1, and the function of lidocaine was related to the regulation of circ_DYNC1H1/miR-520a-3p axis. USP14 served as a target for miR-520a-3p, and circ_DYNC1H1 could sponge miR-520a-3p to regulate the USP14 expression. The lidocaine-induced suppression of HCC development was also achieved by mediating the miR-520a-3p/USP14 axis. In vivo assay revealed that lidocaine suppressed the tumor growth of HCC by reducing the expression of circ_DYNC1H1 to affect the levels of miR-520a-3p and USP14. Our results clarified that lidocaine impeded tumor progression via targeting the circ_DYNC1H1/miR-520a-3p/USP14 axis in HCC cells.

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BEZ235 Increases the Sensitivity of Hepatocellular Carcinoma to Sorafenib by Inhibiting PI3K/AKT/mTOR and Inducing Autophagy

BioMed Research International ◽

10.1155/2021/5556306 ◽

2021 ◽

Vol 2021 ◽

pp. 1-19

Author(s):

Weiya Cao ◽

Xueke Liu ◽

Yinci Zhang ◽

Amin Li ◽

Yinghai Xie ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Cycle ◽

Cell Lines ◽

Acquired Resistance ◽

Inhibitory Effect ◽

Mtor Pathway ◽

Protein Levels ◽

Huh7 Cells

Acquired resistance of hepatocellular carcinoma (HCC) to sorafenib (SFB) is the main reason for the failure of SFB treatment of the cancer. Abnormal activation of the PI3K/AKT/mTOR pathway is important in the acquired resistance of SFB. Therefore, we investigated whether BEZ235 (BEZ) could reverse acquired sorafenib resistance by targeting the PI3K/mTOR pathway. A sorafenib-resistant HCC cell line Huh7R was established. MTT assay, clone formation assay, flow cytometry, and immunofluorescence were used to analyze the effects of BEZ235 alone or combined with sorafenib on cell proliferation, cell cycle, apoptosis, and autophagy of Huh7 and Huh7R cells. The antitumor effect was evaluated in animal models of Huh7R xenografts in vivo. Western blot was used to detect protein levels of the PI3K/AKT/mTOR pathway and related effector molecules. In vitro results showed that the Huh7R had a stronger proliferation ability and antiapoptosis effect than did Huh7, and sorafenib had no inhibitory effect on Huh7R. SFB + BEZ inhibited the activation of the PI3K/AKT/mTOR pathway caused by sorafenib. Moreover, SFB + BEZ inhibited the proliferation and cloning ability, blocked the cell cycle in the G0/G1 phase, and promoted apoptosis in the two cell lines. The autophagy level in Huh7R cells was higher than in Huh7 cells, and BEZ or SFB + BEZ further promoted autophagy in the two cell lines. In vivo, SFB + BEZ inhibited tumor growth by inducing apoptosis and autophagy. We concluded that BEZ235 enhanced the sensitivity of sorafenib through suppressing the PI3K/AKT/mTOR pathway and inducing autophagy. These observations may provide the experimental basis for sorafenib combined with BEZ235 in trial treatment of HCC.

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Apoptotic Effects of Xanthium strumarium via PI3K/AKT/mTOR Pathway in Hepatocellular Carcinoma

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/2176701 ◽

2019 ◽

Vol 2019 ◽

pp. 1-13

Author(s):

Juyoung Kim ◽

Kyung Hee Jung ◽

Hyung Won Ryu ◽

Doo-Young Kim ◽

Sei-Ryang Oh ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Growth ◽

Caspase 3 ◽

Mtor Pathway ◽

Terminal Deoxynucleotidyl Transferase ◽

Mechanistic Study ◽

Migration And Invasion ◽

Xanthium Strumarium ◽

Apoptotic Effects ◽

Hcc Cells

Xanthium strumarium (XS) has been traditionally used as a medicinal herb for treating inflammatory diseases, such as appendicitis, chronic bronchitis, rheumatism, and rhinitis. In this study, we yielded ethanol extracts from XS and investigated whether they could inhibit the progression of hepatocellular carcinoma (HCC) and its underlying mechanism. The XS-5 and XS-6 extracts dose-dependently inhibited the growth and proliferation in HCC cell lines. The apoptotic effects of them were observed via increased levels of cleaved caspase-3 and cleaved PARP, as well as elevated numbers of terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling- (TUNEL-) positive apoptotic cells. They also decreased XIAP and Mcl-1 expression via loss of mitochondrial membrane potential. Additionally, they inhibited the invasion and migration of HCC cells. In an ex vivo model, the extracts significantly inhibited tumor cell growth and induced apoptosis by increasing the expression of the cleaved caspase-3. A mechanistic study revealed that they effectively suppressed PI3K/AKT/mTOR signaling pathways in HCC cells. Taken together, our findings demonstrate that they could efficiently not only induce apoptosis but also inhibit cell growth, migration, and invasion of human HCC cells by blocking the PI3K/AKT/mTOR pathway. We suggest XS-5 and XS-6 as novel natural anti-HCC agents.

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Upregulation of SGOL2 Predicts Poor Prognosis and Facilitates Hepatocellular Carcinoma Progression via Dysregulating the Cell Cycle by Directly Activating MAD2

10.21203/rs.3.rs-560609/v1 ◽

2021 ◽

Author(s):

Qingqing Hu ◽

Xiaochu Hu ◽

Yalei Zhao ◽

Lingjian Zhang ◽

Ya Yang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Cycle ◽

The Cancer Genome Atlas ◽

Loss Of Function ◽

Protein Levels ◽

Cancer Genome Atlas ◽

Centromeric Protein ◽

Hcc Cells

Abstract Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Shugoshin-like protein 2 (SGOL2) is a centromeric protein that ensures the correct and orderly process of mitosis by protecting and maintaining centripetal adhesions during meiosis and mitosis. However, the role of SGOL2 in cancer is not well understood. Methods: The mRNA and protein levels of SGOL2 and survival analysis were conducted in The Cancer Genome Atlas (TCGA) and further validated in 2 independent cohorts. Differential genes correlated with SGOL2 and mitotic arrest deficient 2 like 1 (MAD2) were obtained using LinkedOmics. Subsequently, loss-of-function and rescue assays were carried out in vitro and in vivo to assess the functions of SGOL2 in hepatic tumorigenisis. Findings: We found that SGOL2 was significantly overexpressed in HCC and predicted unfavorable overall survival in HCC patients. Next, we identified 47 differentially expressed genes positively correlated with both SGOL2 and MAD2 to be mainly involved in the cell cycle. In addition, SGOL2 downregulation suppressed the migration, invasion, proliferation, stemness and EMT of HCC cells and inhibited tumorigenesis in vivo. Furthermore, SGOL2 promoted tumor proliferation by activating MAD2-induced cell cycle dysregulation, which could be reversed by the MAD2 inhibitor M2I-1. We also proved that SGOL2 activated MAD2 by directly binding with MAD2. Conclusions: The results of this study showed that SGOL2 acts as an oncogene in HCC cells by directly activating MAD2 and then dysregulating the cell cycle, thereby providing a potential target for HCC patients in the future.

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MiR-199a-modified exosomes from adipose tissue-derived mesenchymal stem cells improve hepatocellular carcinoma chemosensitivity through mTOR pathway

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-019-1512-5 ◽

2020 ◽

Vol 39 (1) ◽

Cited By ~ 14

Author(s):

Guohua Lou ◽

Liang Chen ◽

Caixia Xia ◽

Weina Wang ◽

Jinjin Qi ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Adipose Tissue ◽

Chemotherapeutic Agents ◽

Mtor Pathway ◽

Doxorubicin Treatment ◽

Transmission Electron ◽

Proliferation And Apoptosis ◽

New Strategy ◽

Hcc Cells

Abstract Background MiR-199a-3p (miR-199a) can enhance the chemosensitivity of hepatocellular carcinoma (HCC). Because of the easy degradation of miRNA by direct infusion, effective vehicle-mediated delivery of miR-199a may represent a new strategy for improving HCC chemotherapy. Considering mesenchymal stem cell (MSC)-derived exosomes as promising natural nanovectors for drug and molecule delivery, we aimed to determine whether exosomes from adipose tissue-derived MSCs (AMSCs) could be used to deliver miR-199a and improve HCC chemosensitivity. Methods MiR-199a-modified AMSCs (AMSC-199a) were constructed by miR-199a lentivirus infection and puromycin selection. MiR-199-modified exosomes (AMSC-Exo-199a) were isolated from the supernatant of AMSC-199a and were assessed by transmission electron microscopy, nanoparticle tracking analysis, and flow cytometry analysis. The expression levels of miR-199a in HCC samples, AMSCs, exosomes, and HCC cells were quantified by real-time PCR. The effects of AMSC-Exo-199a on HCC chemosensitivity were determined by cell proliferation and apoptosis assays and by i.v. injection into orthotopic HCC mouse models with doxorubicin treatment. MTOR, p-4EBP1 and p-70S6K levels in HCC cells and tissues were quantified by Western blot. Results AMSC-Exo-199a had the classic characteristics of exosomes and could effectively mediate miR-199a delivery to HCC cells. Additionally, AMSC-Exo-199a significantly sensitized HCC cells to doxorubicin by targeting mTOR and subsequently inhibiting the mTOR pathway. Moreover, i.v.-injected AMSC-Exo-199a could distribute to tumor tissue and markedly increased the effect of Dox against HCC in vivo. Conclusions AMSC-Exo-199a can be an effective vehicle for miR-199a delivery, and they effectively sensitized HCC to chemotherapeutic agents by targeting mTOR pathway. AMSC-Exo-199a administration may provide a new strategy for improving HCC chemosensitivity.

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Loss of miR-100 and miR-125b results in cancer stem cell properties through IGF2 upregulation in hepatocellular carcinoma

Scientific Reports ◽

10.1038/s41598-020-77960-9 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Hyang Sook Seol ◽

Yoshimitsu Akiyama ◽

San-Eun Lee ◽

Shu Shimada ◽

Se Jin Jang

Keyword(s):

Hepatocellular Carcinoma ◽

Stem Cells ◽

Stem Cell ◽

Cancer Stem Cells ◽

Xenograft Model ◽

Mtor Pathway ◽

Carcinoma Cells ◽

Stable Cell Line ◽

Hep3b Cells ◽

Igf2 Expression

AbstractStemness factors control microRNA expression in cancer stem cells. Downregulation of miR-100 and miR-125b is associated with tumor progression and prognosis of various cancers. Comparing miRNA profiling of patient-derived tumorsphere (TS) and adherent (2D) hepatocellular carcinoma cells, miR-100 and miR-125b are identified to have association with stemness. In TS cells, miR-100 and miR-125b were downregulated comparing to 2D cells. The finding was reproduced in Hep3B cells. Overexpression of stemness factors NANOG, OCT4 and SOX2 by introduction of gene constructs in Hep3B cells suppressed these two miRNA expression levels. Treatment of chromeceptin, an IGF signaling pathway inhibitor, decreased numbers of TS and inhibited the AKT/mTOR pathway. Stable cell line of miR-100 and miR-125b overexpression decreased IGF2 expression and inhibited tumor growth in the xenograft model. In conclusion, miR-100 and miR-125b have tumor suppressor role in hepatocellular carcinoma through inhibiting IGF2 expression and activation of the AKT/mTOR pathway.

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LncRNA RHPN1-AS1 Promotes Cell Proliferation, Migration and Invasion Through Targeting miR-7-5p and Activating PI3K/AKT/mTOR Pathway in Hepatocellular Carcinoma

Technology in Cancer Research & Treatment ◽

10.1177/1533033820957023 ◽

2020 ◽

Vol 19 ◽

pp. 153303382095702

Author(s):

Xue-zhen Song ◽

Xiao-ning Ren ◽

Xiao-jun Xu ◽

Xiao-xuan Ruan ◽

Yi-li Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Molecular Mechanism ◽

Cancer Progression ◽

Cell Clone ◽

Mtor Pathway ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Gene Assay ◽

Hcc Cells

Hepatocellular carcinoma (HCC) is a severe disease with high mortality in the world. Emerging evidence has suggested that lncRNAs play an important role in cancer progression, including HCC. This study aimed to comprehensively investigate the effect of lncRNA RHPN1 antisense RNA 1 (RHPN1-AS1) on HCC and its underlying molecular mechanism. In this study, we evaluated the expressions of lncRNA RHPN1-AS1 and miR-7-5p by qRT-RCR in both HCC tissue and HCC cells. Our findings showed that lncRNA RHPN1-AS1 was upregulated in HCC tissue and HCC cells, while miR-7-5p was downregulated. LncRNA RHPN1-AS1 expression in HCC patients was closely related to vascular invasion, tumor-node-metastasis (TNM) stage and barcelona clinic liver cancer (BCLC) stage. Furthermore, we quantified cell clone-formation ability, proliferation, migration and invasion of HCCLM3 and MHCC97 H cells using several assays (colony formation assay, 5-Ethynyl-2′-deoxyuridine (EdU) assay and transwell assay, respectively). Functional experiments confirmed that silencing lncRNA RHPN1-AS1 inhibited cell proliferation, migration and invasion in HCCLM3 and MHCC97 H cells. After that, bioinformatics analysis, dual luciferase reporter gene assay, qRT-PCR and western blot were used to investigate the molecular mechanism of lncRNA RHPN1-AS1 on HCC. Mechanistically, the rescue experiments demonstrated that miR-7-5p inhibitor reversed the inhibition effect of silencing lncRNA RHPN1-AS1 on HCCLM3 cells proliferation, migration and invasion. Moreover, silencing lncRNA RHPN1-AS1 also inhibited the activation of PI3K/AKT/mTOR pathway. Taken together our findings demonstrated that lncRNA RHPN1-AS1 could facilitate cell proliferation, migration and invasion via targeting miR-7-5p and activating PI3K/AKT/mTOR pathway in HCC.

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Modulation of SIRT3 expression through CDK4/6 enhances the anti-cancer effect of sorafenib in hepatocellular carcinoma cells

10.21203/rs.2.16163/v4 ◽

2020 ◽

Author(s):

HanHee Jo ◽

Yusun Park ◽

Taehun Kim ◽

Jisu Kim ◽

JongSook Lee ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Lines ◽

Combined Treatment ◽

Xenograft Model ◽

Cancer Tissue ◽

Sorafenib Treatment ◽

Tumor Types ◽

Related Proteins ◽

Sirt3 Expression ◽

Hcc Cells

Abstract Background : Hepatocellular carcinoma (HCC) is the leading cause of cancer-related deaths worldwide. The only drug currently approved for clinical use in the treatment of advanced HCC is sorafenib. However, many patients with HCC show reduced sensitivity to sorafenib during treatment. SIRT3, a member of the mammalian sirtuin family, is a tumor suppressor in certain tumor types. However, only few studies have investigated the effects of SIRT3 on tumor prognosis and sorafenib sensitivity in patients with HCC. Here, we aimed to investigate the correlation between SIRT3 expression and glucose metabolism and proliferation in HCC and discover effective compounds that increase endogenous SIRT3 modulation effect of sorafenib. Methods: To determine the correlation between SIRT3 and glucose related proteins, immunostaining was performed with liver cancer tissue using various antibodies. To investigate whether the expression of SIRT3 in HCC is related to the resistance to sorafenib, we treated sorafenib after the modulation of SIRT3 levels in HCC cell lines (overexpression in Huh7, knockdown in HepG2). We also employed PD0332991 to modulate the SIRT3 expression in HCC cell and conducted functional assays. Results: SIRT3 expression was downregulated in high glycolytic and proliferative HCC cells of human patients, xenograft model and HCC cell lines. Moreover, SIRT3 expression was downregulated after sorafenib treatment, resulting in reduced drug sensitivity in HCC cell lines. To enhance the anti-tumor effect of sorafenib, we employed PD0332991 (CDK4/6-Rb inhibitor) based on the correlation between SIRT3 and phosphorylated retinoblastoma protein in HCC. Notably, combined treatment with sorafenib and PD0332991 showed an enhancement of the anti-tumor effect in HCC cells. Conclusions: Our data suggest that the modulation of SIRT3 by CDK4/6 inhibition might be useful for HCC therapy together with sorafenib, which, unfortunately, has limited efficacy and whose use is often associated with drug resistance.

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TRIB3 promotes hepatocellular carcinoma growth and predicts poor prognosis

Cancer Biomarkers ◽

10.3233/cbm-201577 ◽

2020 ◽

Vol 29 (3) ◽

pp. 307-315

Author(s):

Xiao-Jun Wang ◽

Fei-Fei Li ◽

Yi-Jing Zhang ◽

Man Jiang ◽

Wan-Hua Ren

Keyword(s):

Hepatocellular Carcinoma ◽

Poor Prognosis ◽

Xenograft Model ◽

Clinicopathological Characteristics ◽

Tissue Samples ◽

Normal Tissues ◽

Related Family ◽

Hcc Cells

BACKGROUND: Tribbles pseudokinase 3 (TRIB3) is a member of the tribbles-related family, which is involved a lot of cellular processes and multiple cancers, such as breast cancer, colorectal cancer, renal cell carcinomas, and lung cancer. However, the expression pattern and biological function of TRIB3 in hepatocellular carcinoma (HCC) has not yet been completely elucidated. METHODS: The expression of TRIB3 and clinicopathological characteristics were evaluated by HCC tissue microarray and qPCR analysis. Lentivirus packaging and transfection were employed to establish cell lines with TRIB3 overexpression or knockdown. The biological functions of TRIB3 in the growth of HCC were determined using MTT and crystal violet assays. Tumor growth was monitored in a xenograft model in vivo. RESULTS: The expression of TRIB3 was upregulated in HCC tissue samples compared to paired normal tissues in 45 patients examined by qPCR assay. TRIB3 expression was significantly correlated with HCC tumor size and prognosis in postoperative patients by analysis of the TRIB3 expression data and HCC clinical features. Forced expression of TRIB3 significantly promoted HCC growth in vitro. In contrast, downregulation of TRIB3 inhibited cell growth in vitro. Moreover, knockdown of TRIB3 suppressed tumorigenesis of HCC cells in vivo. CONCLUSION: TRIB3 promotes growth abilities of HCC cells both in vitro and in vivo and predicts poor prognosis of HCC patients, which serves as a prognostic marker and might provide a potential therapeutic candidate for patients with HCC.

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Indole hydrazide compound ZJQ-24 inhibits angiogenesis and induces apoptosis cell death through abrogation of AKT/mTOR pathway in hepatocellular carcinoma

Cell Death and Disease ◽

10.1038/s41419-020-03108-2 ◽

2020 ◽

Vol 11 (10) ◽

Author(s):

Jing Liu ◽

Ying Liu ◽

Jianqiang Zhang ◽

Dan Liu ◽

Yafeng Bao ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Growth ◽

Scientific Evidence ◽

Flow Cytometric Analysis ◽

Xenograft Model ◽

Mtor Pathway ◽

Flow Cytometric ◽

M Phase

Abstract Angiogenesis and the activation of AKT/mTOR pathway are crucial for hepatocarcinoma development and progression, the activation of mTORC1/2 and relevant substrates have been confirmed in clinical hepatocarcinoma samples. Therefore, AKT/mTOR pathway represents the major targets for anti-cancer drugs development. Here, we investigated the anti-proliferative activity and mechanisms of ZJQ-24 in hepatocellular carcinoma, both in vivo and in vitro. A hepatocellular carcinoma xenograft model showed that ZJQ-24 significantly inhibited tumor growth with few side effects. MTT assays, flow cytometric analysis, Western blotting and immunohistochemistry identified that ZJQ-24 effectively suppressed hepatocellular carcinoma cell proliferation via G2/M phase arrest and caspase-dependent apoptosis but had no cytotoxic on normal cells. Furthermore, ZJQ-24 significantly blocked AKT/mTOR signaling by down-regulation of mTORC1 molecules, including phospho-p70S6K (Thr389) and phospho-4EBP-1 (Ser65, Thr37/46, Thr70) and phospho-AKT (Ser473) in HCC cells. It is very important that the ZJQ-24 did not induce the mTORC1-depdent PI3K/Akt feedback activation through JNK excitation. Moreover, ZJQ-24 inhibited the cap-dependent translation initiation by impairing the assembly of the eIF4E/eIF4G complex. Immunohistochemistry further confirmed ZJQ-24 inhibited the tumor growth through suppression of VEGF and AKT/mTOR pathways in vivo. Thus, the present study is the first to illustrate that ZJQ-24 triggers antiangiogenic activity and apoptosis via inhibiting the AKT/mTOR pathway in hepatocellular carcinoma cells, providing basic scientific evidence that ZJQ-24 shows great potential function as inhibitor of angiogenesis and tumor growth in hepatocellular carcinoma.

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