Alantolactone inhibits cell autophagy and promotes apoptosis through targeting AP2M1 in acute lymphotic leukemia

Abstract Background: Acute lymphoblastic leukemia (ALL) is an aggressive hematopoietic malignancy that is most common in children. Alantolactone (ALT) has been reported to have antitumor activity in different types of cancers. This study aimed to investigate the antitumor activity and molecular mechanism of ALT in ALL. Methods: The ALL cell lines were treated with 1, 5 and 10μM of ALT, and then subjected to MTT assay and RNA sequencing. Flow cytometry, JC-1 staining and immunofluorescence staining assays were employed to measure cell apoptosis and autophagy. Meanwhile, Western blot analysis was used to detect apoptosis and autophagy related proteins. Finally, the effect of ALT on tumor growth was measured in BV173 xenograft nude mouse model. Results: In this study, we demonstrated that ALT inhibited the proliferation of ALL cells in does-dependent manner. A series of experiments demonstrated that ALT inhibited cell proliferation, colony formation, autophagy, induced apoptosis and restained tumor growth in vivo through upregulating adaptor related protein complex 2 subunit mu 1 (AP2M1). Moreover, autophagy activator rapamycin attenuated the pro-apoptotic effect of ALT on BV173 and NALM6 cell lines. Further, overexpressed AP2M1 decreased the expression of Beclin1, LC3-II/LC3-1 ratio and increased p62 expression. Fianally, knockdown of Beclin1 increased the levels of bax, cleaved caspase 3 and cytochrome C and decreased bcl-2 expression. Conclusions: This study demonstrated that ALT exerts antitumor activity through inducing apoptosis and inhibiting autophagy by upregulating AP2M1 in ALL, indicating a potential therapeutic strategy for ALL treatment.

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Alantolactone inhibits cell autophagy and promotes apoptosis via AP2M1 in acute lymphoblastic leukemia

Cancer Cell International ◽

10.1186/s12935-020-01537-9 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Ce Shi ◽

Wenjia Lan ◽

Zhenkun Wang ◽

Dongguang Yang ◽

Jia Wei ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Tumor Growth ◽

Cell Lines ◽

Lymphoblastic Leukemia ◽

Dependent Manner ◽

Nude Mouse Model ◽

Hematopoietic Malignancy ◽

Induced Apoptosis ◽

Anti Tumor Activity

Abstract Background Acute lymphoblastic leukemia (ALL) is an aggressive hematopoietic malignancy that is most commonly observed in children. Alantolactone (ALT) has been reported to exhibit anti-tumor activity in different types of cancer. The aim of the present study was to investigate the anti-tumor activity and molecular mechanism of ALT in ALL. Methods ALL cell lines were treated with 1, 5 and 10 μM ALT, and cell viability was assessed using an MTT assay and RNA sequencing. Flow cytometry, JC-1 staining and immunofluorescence staining assays were used to measure cell apoptosis and autophagy. Additionally, western blot analysis was used to detect expression of apoptosis and autophagy related proteins. Finally, the effects of ALT on tumor growth were assessed in a BV173 xenograft nude mouse model. Results ALT inhibited the proliferation of ALL cells in a dose-dependent manner. Additionally, it was demonstrated that ALT inhibited cell proliferation, colony formation, autophagy, induced apoptosis and reduced tumor growth in vivo through upregulating the expression of adaptor related protein complex 2 subunit mu 1 (AP2M1). Moreover, the autophagy activator rapamycin, attenuated the pro-apoptotic effects of ALT on BV173 and NALM6 cell lines. Overexpression of AP2M1 decreased the expression of Beclin1 and the LC3-II/LC3-1 ratio, and increased p62 expression. Knockdown of Beclin1 increased the levels of bax, cleaved caspase 3 and cytochrome C, and decreased bcl-2 expression. Conclusions The present study demonstrated that ALT exerts anti-tumor activity through inducing apoptosis and inhibiting autophagy by upregulating AP2M1 in ALL, highlighting a potential therapeutic strategy for treatment of ALL.

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Alantolactone inhibits cell autophagy and promotes apoptosis via AP2M1 in acute lymphoblastic leukemia

10.21203/rs.3.rs-21650/v3 ◽

2020 ◽

Author(s):

Ce Shi ◽

Wenjia Lan ◽

Zhenkun Wang ◽

Dongguang Yang ◽

Jia Wei ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Tumor Growth ◽

Cell Lines ◽

Lymphoblastic Leukemia ◽

Dependent Manner ◽

Nude Mouse Model ◽

Hematopoietic Malignancy ◽

Induced Apoptosis ◽

Anti Tumor Activity

Abstract Background: Acute lymphoblastic leukemia (ALL) is an aggressive hematopoietic malignancy that is most commonly observed in children. Alantolactone (ALT) has been reported to exhibit anti-tumor activity in different types of cancer. The aim of the present study was to investigate the anti-tumor activity and molecular mechanism of ALT in ALL. Methods: ALL cell lines were treated with 1, 5 and 10 μM ALT, and cell viability was assessed using an MTT assay and RNA sequencing. Flow cytometry, JC-1 staining and immunofluorescence staining assays were used to measure cell apoptosis and autophagy. Additionally, western blot analysis was used to detect expression of apoptosis and autophagy related proteins. Finally, the effects of ALT on tumor growth were assessed in a BV173 xenograft nude mouse model. Results: ALT inhibited the proliferation of ALL cells in a dose-dependent manner. Additionally, it was demonstrated that ALT inhibited cell proliferation, colony formation, autophagy, induced apoptosis and reduced tumor growth in vivo through upregulating the expression of adaptor related protein complex 2 subunit mu 1 (AP2M1). Moreover, the autophagy activator rapamycin, attenuated the pro-apoptotic effects of ALT on BV173 and NALM6 cell lines. Overexpression of AP2M1 decreased the expression of Beclin1 and the LC3-II/LC3-1 ratio, and increased p62 expression. Knockdown of Beclin1 increased the levels of bax, cleaved caspase 3 and cytochrome C, and decreased bcl-2 expression. Conclusions: The present study demonstrated that ALT exerts anti-tumor activity through inducing apoptosis and inhibiting autophagy by upregulating AP2M1 in ALL, highlighting a potential therapeutic strategy for treatment of ALL.

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Isoquinolinamine FX-9 Exhibits Anti-Mitotic Activity in Human and Canine Prostate Carcinoma Cell Lines

International Journal of Molecular Sciences ◽

10.3390/ijms20225567 ◽

2019 ◽

Vol 20 (22) ◽

pp. 5567

Author(s):

Jan Torben Schille ◽

Ingo Nolte ◽

Eva-Maria Packeiser ◽

Laura Wiesner ◽

Jens Ingo Hein ◽

...

Keyword(s):

Cell Lines ◽

Lymphoblastic Leukemia ◽

Leukemia Cell ◽

In Vivo Studies ◽

Mediated Effects ◽

Multinucleated Cells ◽

Prostate Carcinoma Cell ◽

Castrate Resistant ◽

Induced Apoptosis

Current therapies are insufficient for metastatic prostate cancer (PCa) in men and dogs. As human castrate-resistant PCa shares several characteristics with the canine disease, comparative evaluation of novel therapeutic agents is of considerable value for both species. Novel isoquinolinamine FX-9 exhibits antiproliferative activity in acute lymphoblastic leukemia cell lines but has not been tested yet on any solid neoplasia type. In this study, FX-9′s mediated effects were characterized on two human (PC-3, LNCaP) and two canine (CT1258, 0846) PCa cell lines, as well as benign solid tissue cells. FX-9 significantly inhibited cell viability and induced apoptosis with concentrations in the low micromolar range. Mediated effects were highly comparable between the PCa cell lines of both species, but less pronounced on non-malignant chondrocytes and fibroblasts. Interestingly, FX-9 exposure also leads to the formation and survival of enlarged multinucleated cells through mitotic slippage. Based on the results, FX-9 acts as an anti-mitotic agent with reduced cytotoxic activity in benign cells. The characterization of FX-9-induced effects on PCa cells provides a basis for in vivo studies with the potential of valuable transferable findings to the benefit of men and dogs.

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Id1 is a common downstream target of oncogenic tyrosine kinases in leukemic cells

Blood ◽

10.1182/blood-2007-07-103010 ◽

2008 ◽

Vol 112 (5) ◽

pp. 1981-1992 ◽

Cited By ~ 30

Author(s):

Winnie F. Tam ◽

Ting-Lei Gu ◽

Jing Chen ◽

Benjamin H. Lee ◽

Lars Bullinger ◽

...

Keyword(s):

Cell Lines ◽

Tyrosine Kinases ◽

Target Genes ◽

Bone Marrow Cells ◽

Leukemic Cells ◽

Hematopoietic Malignancy ◽

Downstream Target ◽

Models Of Disease ◽

Induced Apoptosis

Abstract Oncogenic tyrosine kinases, such as BCR-ABL, TEL-ABL, TEL-PDGFβR, and FLT3-ITD, play a major role in the development of hematopoietic malignancy. They activate many of the same signal transduction pathways. To identify the critical target genes required for transformation in hematopoietic cells, we used a comparative gene expression strategy in which selective small molecules were applied to 32Dcl3 cells that had been transformed to factor-independent growth by these respective oncogenic alleles. We identified inhibitor of DNA binding 1 (Id1), a gene involved in development, cell cycle, and tumorigenesis, as a common target of these oncogenic kinases. These findings were prospectively confirmed in cell lines and primary bone marrow cells engineered to express the respective tyrosine kinase alleles and were also confirmed in vivo in murine models of disease. Moreover, human AML cell lines Molm-14 and K562, which express the FLT3-ITD and BCR-ABL tyrosine kinases, respectively, showed high levels of Id1 expression. Antisense and siRNA based knockdown of Id1-inhibited growth of these cells associated with increased p27Kip1 expression and increased sensitivity to Trail-induced apoptosis. These findings indicate that Id1 is an important target of constitutively activated tyrosine kinases and may be a therapeutic target for leukemias associated with oncogenic tyrosine kinases.

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Cytotoxic effect of Montivipera bornmuelleri’s venom on cancer cell lines: in vitro and in vivo studies

PeerJ ◽

10.7717/peerj.9909 ◽

2020 ◽

Vol 8 ◽

pp. e9909

Author(s):

Carol Haddoub ◽

Mohamad Rima ◽

Sandrine Heurtebise ◽

Myriam Lawand ◽

Dania Jundi ◽

...

Keyword(s):

Tumor Growth ◽

Cell Lines ◽

Cytotoxic Effect ◽

In Vivo Studies ◽

Dependent Manner ◽

In Vivo Testing ◽

Murine Fibrosarcoma ◽

Dose Dependent

Background Montivipera bornmuelleri’s venom has shown immunomodulation of cytokines release in mice and selective cytotoxicity on cancer cells in a dose-dependent manner, highlighting an anticancer potential. Here, we extend these findings by elucidating the sensitivity of murine B16 skin melanoma and 3-MCA-induced murine fibrosarcoma cell lines to M. bornmuelleri’s venom and its effect on tumor growth in vivo. Methods The toxicity of the venom on B16 and MCA cells was assessed using flow cytometry and xCELLigence assays. For in vivo testing, tumor growth was followed in mice after intratumoral venom injection. Results The venom toxicity showed a dose-dependent cell death on both B16 and MCA cells. Interestingly, overexpression of ovalbumin increased the sensitivity of the cells to the venom. However, the venom was not able to eradicate induced-tumor growth when injected at 100 µg/kg. Our study demonstrates a cytotoxic effect of M. bornmuelleri’s venom in vitro which, however, does not translate to an anticancer action in vivo.

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Studies of pemetrexed and gemcitabine, alone and in combinations, in human lung cancer models

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.17114 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 17114-17114 ◽

Cited By ~ 2

Author(s):

D. C. Chan ◽

V. J. Chen ◽

Z. Zhang ◽

B. Helfrich ◽

F. R. Hirsch ◽

...

Keyword(s):

Tumor Growth ◽

Cell Lines ◽

In Vivo Studies ◽

Human Lung Cancer ◽

Dependent Manner ◽

Antitumor Effects ◽

Nude Rats ◽

Combination Regimens

17114 Background: Gemcitabine (GEM) is a deoxycytidine analog that inhibits DNA synthesis. Pemetrexed (ALIMTA, PEM) is a novel antifolate inhibiting multiple enzymes targets, including thymidylate synthase (TS). This study aimed at evaluating the antitumor effects of these antimetabolites against NSCLC and SCLC tumor models. Methods: In vitro growth inhibition (IC50) studies were done by 6-days MTT assays against a panel of 20 NSCLC and 17 SCLC cell lines. In vivo studies used only NSCLC H2122 tumor line, implanted either subcutaneously in athymic nude mice or orthotopically in athymic nude rats. Drugs were given via the ip route at the designated schedules. Results: Against NSCLC and SCLC cell lines, the averaged IC50s of GEM were 0.015 ± 0.008 μM and 0.055 ± 0.04 μM respectively. The corresponding averaged IC50s for PEM were 0.65 ± 0.2 μM and 0.091±0.018 μM respectively. When H2122 tumors reached 50–100mg, mice were treated with 10 daily doses of PEM at 100, 200 and 300 mg/kg, or three doses of GEM every 4 days at 30, 60 and 120 mg/kg. PEM delayed tumor growth by 12 to 18 days, and GEM delayed by 10 to 14 days, relative to vehicle control. Results of three combination regimens with GEM (30 mg/kg) and PEM (100 mg/kg) were: (1) GEM → PEM gave intermediate activities between the two single agents, but was toxic to animals; (2) PEM and GEM given concurrently were more active than single agents alone and delayed tumor growth by 12 days with some toxic side effects; (3) PEM → GEM was better than the single agents alone, and delayed tumor growth by ∼14 days without toxicity. Athymic nude rats bearing orthotopic H2122 tumors given PEM daily at 50, 100 and 200 mg/kg for 21 days had significantly prolonged survival, but not in a dose-dependent manner. PEM at 50 mg/kg was more effective than doses at 100 or 200 mg/kg. GEM was toxic to nude rats due to poor plasma deamination of GEM. Conclusions: In vitro, PEM was more potent against SCLC than NSCLC cell lines, but GEM had similar activities against all lung lines tested. Studies of H2122 xenografts in rodent supported PEM → GEM as the preferred sequence for the combined administration of these two drugs. [Table: see text]

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Characterization of the Effects of Pim Kinase Inhibition on Multiple Oncogene-Driven Cell Lines

Blood ◽

10.1182/blood.v112.11.2662.2662 ◽

2008 ◽

Vol 112 (11) ◽

pp. 2662-2662

Author(s):

Stefan David Gross ◽

John E Robinson ◽

Shelley Allen ◽

April Cox ◽

Walt E DeWolf ◽

...

Keyword(s):

Tumor Growth ◽

Cell Line ◽

Protein Kinases ◽

Cell Lines ◽

Biological Effects ◽

Xenograft Model ◽

Dependent Manner ◽

Kinase Inhibition ◽

In Cells

Abstract We report here the biological effects of inhibiting Pim-1, -2 and -3 serine/threonine protein kinases in cells and in vivo using a novel, potent and selective small molecule inhibitor directed against these kinases. In vitro enzyme assays revealed potent inhibition of all three Pim kinase isoforms while maintaining selectivity against more than 220 other protein kinases. In cells, compound treatment produced biological effects consistent with Pim inhibition, including a reduction in BAD protein phosphorylation. Moreover, this biological activity corresponds well with the compound’s anti-proliferative and pro-apoptotic activity in the IL-3 dependent mouse pro-B cell line Ba/F3 and in factor-indpendent Ba/F3 cell lines dependent upon the expression of BCR-Abl or TEL-JAK2 for growth and survival. Importantly, compared to the BCR-Abl driven Ba/F3 cell line, this compound was equally effective at blocking the growth of an Imatinib-resistant BCR-Abl[ T315I]-driven Ba/F3 cell line. Finally, this compound possesses pharmacokinetic properties that predict the potential for in vivo activity. Therefore, we assessed the effect of Pim kinase inhibition on tumor growth in a mouse subcutaneous tumor xenograft model employing a cell line driven by the TEL-JAK2 oncogene. Results demonstrated that the compound significantly inhibited tumor growth in a dose-dependent manner. In terms of potential clinical utility, these data show that Pim kinase inhibition could be an effective therapeutic strategy for numerous hematologic malignancies including chronic and acute myelogenous leukemias, particularly in those patients that have become resistant to existing therapies such as Imatinib.

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Overexpression of Notch1 Inducing T-ALL Phenotype and Promoting Angiogenesis in Zebrafish

Blood ◽

10.1182/blood.v128.22.5276.5276 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5276-5276

Author(s):

Lijing Shen ◽

Fangyuan Chen ◽

Kai Qing ◽

Xiang LI ◽

Haiyan LIU

Keyword(s):

Cell Lines ◽

Peripheral Blood ◽

Blood Smear ◽

Conflicts Of Interest ◽

Lymphoblastic Leukemia ◽

Control Group ◽

Transgenic Zebrafish ◽

Poor Prognostic Factor ◽

Induced Apoptosis

Abstract Aim: Abnormal activated Notch1 gene is familiar to us as a poor prognostic factor in T cell acute lymphoblastic leukemia (T-ALL). This in vivo study aimed to establish a stable line of zebrafish overexpressing the human Notch1 gene under the control of a heat stress-inducible promoter, and explore its roles in etiology of T-ALL, and in tumor-related angiogenic process. Methods: Rag2-ICN1(intracellular domain Notch1)-RFP Plasmid was constructed and injected into the embryos Tg (fli1-EGFP) in the one cell stage to construct the double-fluorescence tracer and double transgenic zebrafish, named as Tg(ICN1:RFP/fli1:EGFP). Expression of ICN1 gene and its influence on zebrafish were assayed through fluorescence microscope, RT-PCR, western-blot, FCM, blood smear, RFQ-PCR and drug treatment. Results: Twenty of the 867 (2.3%) mosaic F0 zebrafish embryos were identified to be the germline transgenic zebrafish, including 9 males and 11 females. FCM and peripheral blood smears suggested a significant reduction in the proportion of red blood cells and a increasing of lymphocyte ratio in transgenic zebrafish as compared to control group. RFQ-PCR shows that lymphocytic regulatory factor ikaros, rag1 and lck were significantly reduced, indicates obvious differentiation obstacle in lymphoid lineages. These results were absolutely consistent with the results of FCM and peripheral blood smear. Quercetin suppressed the proliferation activity of T-ALL cell lines and induced apoptosis in a time- and dose-dependent way, meanwhile, quercetin can inhibited Notch1, Hes1, Dll4 and VEGF gene and these proteins expression in A3 and Molt-4 cells (T-ALL cell line). Furthermore, quercetin displayed a significantly reduction in the length of ISV and SIVs in Tg(rag2-ICN1-RFP/fli1-EGFP) zebrafish). Conclusions: The above results induced by overexpression of Notch1 gene closely resemble the main aspects of human T-ALL, suggesting that Notch1 plays a role in the etiology of AML. Some key lymphocytic regulatory factors were apparently changed, which indicates obvious differentiation obstacle in lymphoid lineages and accompanied with the increasing small lymphocytes and precursors. Quercetin inhibited the proliferation and induced apoptosis of T-ALL cell lines as well as inhibition of zebrafish angiogenesis by downregulating the expression of Dll4/Notch1 and VEGF pathways. Therefore, this Notch1 transgenic zebrafish model facilitates dissection of Notch1-mediated signaling in vivo, and enables high-throughput scale screens to identify the potential therapeutic targets. Disclosures No relevant conflicts of interest to declare.

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Perifosine, an Oral Bioactive Novel Akt Inhibitor, Induces In Vitro and In Vivo Antitumor Activity in Waldenstrom Macroglobulinemia.

Blood ◽

10.1182/blood.v108.11.2488.2488 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2488-2488 ◽

Cited By ~ 1

Author(s):

Xavier Leleu ◽

Xiaoying Jia ◽

Anne-Sophie Moreau ◽

Evdoxia Hatjiharisi ◽

Hai Ngo ◽

...

Keyword(s):

Flow Cytometry ◽

Antitumor Activity ◽

Dna Synthesis ◽

Cell Lines ◽

Akt Pathway ◽

Low Grade ◽

Akt Inhibitor ◽

Induced Apoptosis

Abstract Background: Waldenstrom’s Macroglobulinemia (WM) is a low-grade lymphoplasmacytic lymphoma with limited options of therapy. The PI3k/Akt pathway is a critical regulator of cell survival. Our previous studies using proteomic analysis have demonstrated upregulation of members of the PI3k/Akt pathway in WM. We examined whether the new Akt inhibitor perifosine (NSC 639966; Keryx, NY) induces cytotoxicity in WM. Methods: WM cell lines (BCWM1 and WSU-WM) and IgM secreting low-grade lymphoma cell lines (MEC1, RL) were used. Primary CD19+ malignant cells were obtained from patients after informed consent. Inhibition of proliferation was measured using the MTT assay; DNA synthesis was measured using the thymidine uptake assay and apoptosis using Apo2.7 flow cytometry. Bone marrow stromal cells (BMSC) confer growth and resistance to conventional treatments. We therefore, tested the effect of perifosine on WM cells co-cultured with BMSC. Immunoblotting for signaling pathways was performed at different time (30 minutes to 16 hrs) and doses of therapy. In vivo activity of perifosine was assessed using a SCID-irradiated model with subcutaneous tumors in which perifosine was administered by oral gavage daily (35 mg/kg/day). A two-sided t-test was used to determine statistical differences. Results: Perifosine inhibited phosphorylation of Akt in a dose- and time- dependent fashion, as well as downstream GSK3a/b and ribosomal phospho-S6. Perifosine inhibited Akt activity as confirmed by Akt kinase assay. Perifosine induced significant cytotoxicity and inhibition of DNA synthesis with an IC50 of 5-20uM in all cell lines tested. Similar effects were observed in primary CD19+ patient WM cells. Perifosine induced apoptosis in WM cells as demonstrated by flow cytometry. The mechanism of apoptosis induced by perifosine was through activation of SAPK/JNK pathway, followed by caspase-8, -9 and PARP cleavage. The JNK inhibitor SP600125 abrogated perifosine-induced apoptosis. The growth inhibitory effects of perifosine were significant even in the presence of BMSC, IL-6 and IGF-1, which induce resistance to conventional therapies. Importantly, perifosine did not induce cytotoxicity in healthy donor peripheral blood mononuclear cells or in hematopietic stem cells in a methylcellulose colony forming cell assay, indicating lack of toxicity on normal cells. Interestingly, MAPK members such as MEK/ERK were activated by perifosine. The MEK inhibitor U0126 significantly enhanced perifosine-induced cytotoxicity in WM cells, indicating that this combination may be synergistic in vivo. Finally, perifosine induced significant reduction in WM tumor growth in vivo, as compared to control cohort treated with vehicle only at week 6 (p=0.05). Conclusion: Perifosine has significant antitumor activity in WM both in vitro and in vivo. These results provide the framework for clinical evaluation of perifosine in WM. Supported in part by the Leukemia and Lymphoma Society, the Lymphoma Research Foundation and an American Society of Hematology Scholar Award. * XL and XJ are co-first authors.

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Dioscorea Zingiberensis New Saponin Inhibits the Growth of Hepatocellular Carcinoma by Suppressing the Expression of Long Non-coding RNA TCONS-00026762

Frontiers in Pharmacology ◽

10.3389/fphar.2021.678620 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xing Liu ◽

Pingsheng Zhou ◽

Keqing He ◽

Zhili Wen ◽

Yong Gao

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Growth ◽

Cell Lines ◽

Function Analysis ◽

Underlying Mechanism ◽

Dependent Manner ◽

Hcc Cells

Background: The etiology and carcinogenesis of hepatocellular carcinoma (HCC) are associated with various risk factors. Saponins extracted from Dioscorea zingiberensis C. H. Wright exhibit antitumor activity against HCC. This study aimed to investigate the effect and the underlying mechanism of Dioscorea Zingiberensis new saponin (ZnS) on HCC.Methods: Human HCC cell lines, Huh7 and SMMC-7721, were treated with different concentrations of ZnS. Cell apoptosis was determined via flow cytometry assay. Differentially expressed lncRNAs (DElncRNAs) in ZnS-treated SMMC-7721 cells were determined through RNA-sequence. The role of lncRNA TCONS-00026762 in HCC was investigated gain of function analysis, along with cell proliferation, apoptosis, and invasion in HCC cells. A subcutaneous xenograft of SMMC-7721 cell lines was established to study the effects of TCONS-00026762 in vivo. The expression of apoptosis-related proteins was detected in vivo and in vitro via western blotting.Results: ZnS inhibited the proliferation of HCC cell in a dose-dependent manner. ZnS could induce apoptosis in HCC cells. Illumina sequencing results showed that 493 DElncRNAs were identified in ZnS-treated SMMC-7721 cells. TCONS-00026762 expression was down-regulated in the ZnS-treated SMMC-7721 cells. TCONS-00026762 inhibited the effect of ZnS on the proliferation, apoptosis, and invasion of HCC cells. ZnS inhibited the tumor growth, while, TCONS-00026762 promoted tumor growth in vivo. Furthermore, ZnS and TCONS-00026762 regulated cell apoptotic pathways.Conclusion: ZnS significantly inhibits the viability, apoptosis, invasion, and tumorigenicity of HCC cells by regulating the expression of TCONS-00026,762. Our findings provide novel insights into the potential role of lncRNA in HCC therapy.

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