Induced Cell Apoptosis Research Articles

Improved camptothecin encapsulation and efficacy by environmentally sensitive block copolymer/chitosan/fucoidan nanoparticles for targeting lung cancer cells

In this study, thermo-sensitive poly(N-isopropyl acrylamide) (PNP) was polymerized with pH-sensitive poly(acrylic acid) (PAA) to prepare a PAA-b-PNP block copolymer. Above its cloud point, the block copolymer self-assembled into nanoparticles (NPs), encapsulating the anticancer drug camptothecin (CPT) in situ. Chitosan (CS) and fucoidan (Fu) further modified these NPs, forming Fu-CPT-NPs to enhance biocompatibility, drug encapsulation efficiency (EE), and loading content (LC), crucially facilitating P-selectin targeting of lung cancer cells through a drug delivery system. The EE and LC reached 82 % and 3.5 %, respectively. According to transmission electron microscope observation, these Fu-CPT-NPs had uniform spherical shapes with an average diameter of ca. 250 nm. They could maintain their stability in a pH range of 5.0–6.8. In vitro experimental results revealed that the Fu-CPT-NPs exhibited good biocompatibility and had anticancer activity after encapsulating CPT. It could deliver CPT to cancer cells by targeting P-selectin, effectively increasing cell uptake and inducing cell apoptosis. Animal study results showed that the Fu-CPT-NPs inhibited lung tumor growth by increasing tumor cell apoptosis without causing significant tissue damage related to generating reactive oxygen species in lung cancer cells. This system can effectively improve drug-delivery efficiency and treatment effects and has great potential for treating lung cancer.

Preliminary study on cytotoxicity of selegiline on different cancer cell lines: exploration of the induction of ROS-independent apoptosis in breast cancer cells.

The concept of drug repurposing is now widely utilized by biomedical scientists for drug discovery. An example of this is the use of selegiline (SEL), a monoamine oxidase inhibitor that was initially used for the management of depression but is now being considered for another purpose. This study compares the cytotoxic effects of SEL on different cancer cells. Further, the study explores the molecular mechanism of cell death, validating the possibility of its repurposing for cancer. Preliminary analysis of network pharmacological data was conducted in silico, followed by in vitro cytotoxicity tests on PC12, G361, MDA-MB231, MCF7, THP-1, and Hela cells under normoxic and hypoxic conditions, using the MTT assay. The mechanism of cell death was then confirmed by performing DAPI and FITC-conjugated Annexin V and Propidium Iodide (PI) staining assays. Additionally, ROS levels and PKC phosphorylation were also evaluated. In silico analysis has revealed that SEL is associated with ten genes linked to different cancer types. Specifically, SEL was most cytotoxic to neuronal pheochromocytoma, triple-negative human epithelial breast cancer cells, and ER+ and PR+ breast cancer cells. Furthermore, it was observed that this cell death occurred through ROS-independent apoptosis pathways. In addition, SEL was found to inhibit the phosphorylation of PKC, which may contribute to cell death. SEL induces apoptosis in breast cancer cells independently of reactive oxygen species and inhibits the phosphorylation of protein kinase C, which merits further exploration.

Cancer Chemopreventive Effect of 2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone on Diethylnitrosamine-Induced Early Stages of Hepatocarcinogenesis in Rats.

2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC) is a major compound in Cleistocalyx nervosum seed extract (CSE), which has been reported to have various biological activities, including anti-cancer activity. Therefore, this study attempted to evaluate whether DMC is a chemopreventive compound in CSE. Moreover, the preventive mechanisms of CSE and DMC in the DEN-induced early stages of hepatocarcinogenesis in rats were investigated. Male Wistar rats were intraperitoneally injected with DEN 50 mg/kg bw once a week for 8 weeks. Rats received CSE and DMC orally throughout the experiment. The number of glutathione S-transferase placental form (GST-P)-positive foci in the liver was measured. Furthermore, the preventive mechanisms of CSE and DMC on DEN-induced HCC, including cell proliferation and apoptosis, were investigated. Administering CSE at a dosage of 400 mg/kg bw and DMC at a dosage of 10 mg/kg bw significantly decreased the number and size of GST-P-positive foci and GST-P expression. In addition, DMC inhibited the development of preneoplastic lesions by decreasing cell proliferation and causing cell apoptosis; however, CSE inhibited the development of preneoplastic lesions by inducing cell apoptosis. In conclusion, DMC exhibited a cancer chemopreventive effect on the early stages of hepatocarcinogenesis by increasing cell apoptosis and reducing cell proliferation.

Retraction: A InIII‐MOF with Imidazole Decorated Pores as 5‐Fu Delivery System to Inhibit Colon Cancer Cells Proliferation and Induce Cell Apoptosis in vitro and in vivo

Retraction: A In^III‐MOF with Imidazole Decorated Pores as 5‐Fu Delivery System to Inhibit Colon Cancer Cells Proliferation and Induce Cell Apoptosis in vitro and in vivo

Design, synthesis, crystal structure and anticancer activity of organotin(IV)-rhein carboxylates

Two new rhein-organotin complexes Ph3Sn(O2CC14H7O4) (RS01) and Cy3Sn(O2CC14H7O4) (RS02) were synthesized and characterized by elemental analysis, IR, 1H NMR, 13C NMR, 119 Sn NMR, X-ray crystallography and thermo-gravimetric analysis. Both complexes has a triclinic crystal system P-1 space group and one-dimensional supramolecular chain structure. The MTT results demonstrated that rhein's anticancer activity was effectively increased by introducing organotin, RS01 and RS02 exhibited excellent anticancer activity in vitro, significantly superior to cisplatin and mitoxantrone. Interestingly, despite the fact that RS01 and mitoxantrone share the same 9,10-anthraquinone scaffold structure, RS01 not only showed high anticancer activity but also much lower nephrotoxicity than mitoxantrone. Flow cytometry showed that RS01 could significantly induce cell apoptosis and arrest cell cycle in G2 phase. Molecular docking and UV–Vis absorption spectra suggested that RS01 may be intercalation with DNA. Furthermore, western blot results showed that RS01 activated the DNA damage critical protein γ-H2AX and regulated the expression level of the mitochondrial apoptotic pathway critical protein (Bax/Bcl-2). Thus, RS01 induced cell death may be mediated through DNA damage and mitochondrial pathways. As a result, RS01 has significant development and application potential as an anticancer agent.

Retinoic acid receptor-related orphan receptor alpha and synthetic RORα agonist against invasion and metastasis in tongue squamous cell carcinoma

Retinoic acid receptor-related orphan receptor alpha (RORα), an essential tumor suppressor in a range of human malignancies, is classified as a member of the orphan nuclear receptor family. The most prevalent form of oral cancer, tongue squamous cell carcinoma (TSCC) is characterized by its severe malignancy and unfavorable prognosis. However, the extent to which its tumorigenesis mechanisms are associated with RORα expression levels is still not fully understood. The objective of this study was to examine the molecular mechanisms by which RORα is involved in TSCC. Through the use of immunohistochemistry (IHC), it was discovered that the expression level of RORα was significantly downregulated in TSCC tissues when compared to adjacent normal tissues in this study. To further investigate the role of RORα in TSCC, we activated the expression of RORα in human TSCC cell line (SCC9 cells) by transfecting RORα cDNA and using the selective RORα agonist SR1078. The results show that RORα can significantly inhibit the invasion, migration, proliferation, and adhesion of TSCC cells and induce cell apoptosis. In addition, xenograft models confirmed the conclusion that stable activation or treatment with SR1078 to increase RORα content significantly inhibited tumor growth and development. Taken together, this study provides solid evidence for the inhibitory role of RORα in the progression of TSCC. In addition, the preliminary application results of SR1078 in TSCC show that SR1078 is expected to be a potential therapeutic medication for TSCC. These findings provide innovative perspectives on the development of potential biomarkers and agents for TSCC therapy. The objective is to introduce novel strategy and alternatives for the prevention and treatment of TSCC.

Discovery, Synthesis, and Activity Evaluation of Novel Five-Membered Sulfur-Containing Heterocyclic Nucleosides as Potential Anticancer Agents In Vitro and In Vivo.

A series of novel five-membered sulfur-containing heterocyclic nucleoside derivatives were designed, synthesized, and evaluated for their anticancer activities in vitro and in vivo. The structure-activity relationship studies revealed that some of them showed obvious antitumor activities in several cancer cell lines. Among them, compound 22o exhibited remarkable antiproliferative activity against HeLa cells and was more potent than cisplatin (IC50 = 2.80 vs 7.99 μM). Furthermore, mechanism studies indicated that 22o inhibited cell metastasis, induced cell apoptosis, decreased mitochondrial membrane potential, and activated autophagy through the PI3K-Akt-mTOR signaling pathway. Moreover, drug affinity responsive target stability and the cellular thermal shift assay revealed that 22o targeted RPS6 and inhibited its phosphorylation. Importantly, 22o inhibited the growth of the HeLa xenograft mouse model with a low systemic toxicity. These results indicated that 22o may serve as potent anticancer agents that merit further attention in future anticancer drug discovery.

Cellular communication network 1 promotes CASP2 mRNA expression but suppresses its protein translation in esophageal adenocarcinoma.

Induction of apoptosis in tumor cells is one of the best ways to cure cancer. While most apoptosis requires a chain of caspase activation, CASP2 can do this all by itself. The matricellular protein cellular communication network 1 (CCN1) is known for supporting some cancer growth but suppressing others. Esophageal adenocarcinoma (EAC) belongs to the latter. CCN1 is capable of inducing TRAIL-mediated apoptosis in EAC cells. This study found that CCN1 upregulated CASP2 transcription but not its translation in EAC cells because, on one hand, CCN1 downregulated p16 and p21, which increased RB1 phosphorylation allowing E2F1 to transcribe more CASP2 mRNA, on the other hand, CCN1 also upregulated HuR, which is bound to CASP2 mRNA species and blocked its protein translation. As a result, CASP2 contributed nothing to CCN1-induced EAC cell apoptosis. On the contrary, CCN1 promoted CASP3, not only in its transcription but also in its translation and activation, which established the basis for CCN1-induced EAC cell apoptosis.

A novel trifluoromethyl quinoline derivative targeting SGK1 inducing autophagy and apoptosis via regulating mTOR/FOXO3a pathway in glioblastoma

Glioblastoma (GBM) is known for its aggressive nature and poor prognosis, with currently no effective treatment available. Research has shown that introducing fluorinated functional groups into different parts of natural product quinoline significantly affects its anti-tumor activity. Therefore, this study synthesized the trifluoromethyl quinoline derivative FKL296 to investigate its anti-tumor effect on GBM and reveal its mechanism of action. In vitro and in vivo studies have shown that FKL296 effectively inhibitd the growth of GBM and is relatively safe and low toxicity, whice also induced cell apoptosis and autophagy. Additionally, protein kinase profiling and molecular docking analyses have revealed a strong binding affinity between FKL296 and SGK1. Cellular thermal shift assay experiments have confirmed the targeting of SGK1 by FKL296 and its role in enhancing SGK1 stability. Bioinformatics analysis and pathway validation indicated that FKL296 targeted SGK1 and inhibited autophagy in tumor cells through the mTOR/FOXO3a signaling pathway. In summary, FKL296 may become a promising drug for the treatment of GBM.

Aldehyde dehydrogenase 2 family member repression promotes colorectal cancer progression by JNK/p38 MAPK pathways-mediated apoptosis and DNA damage.

Aldehyde (ALDH2) dysfunction has been verified to contribute to human cancers. To investigate the molecular mechanism and biological function of ALDH2 in colorectal cancer (CRC) progression. Human CRC cells with high expression of ALDH2 were screened. After shRNA ALDH2 (sh-ALDH2) transfection, phenotypes [proliferation, apoptosis, acetaldehyde (ACE) accumulation, DNA damage] of CRC cells were verified using cell counting kit-8, flow cytometry, ACE assay, and comet assays. Western blotting was used for evaluation of the apoptosis proteins (Bax and Bcl-2) and JNK/p38 MAPK pathway-associated proteins. We subjected CVT-10216 (a selective ALDH2 inhibitor) to nude mice for establishment of SK-CO-1 mouse xenograft model and observed the occurrence of CRC. The inhibition of ALDH2 could promote the malignant structures of CRC cells, including apoptosis, ACE level, and DNA damage, and cell proliferation was decreased in the sh-ALDH2 group, whereas ALDH2 agonist Alda-1 reversed features. ALDH2 repression can cause ACE accumulation, whereas ACE enhanced CRC cell features related to increased DNA damage. Additionally, ALDH2 repression led to JNK/P38 MAPK activation, and apoptosis, ACE accumulation, and DNA damage were inhibited after p38 MAPK inhibitor SB203580 and JNK inhibitor SP600125 addition. ACE accumulation and raised DNA damage were recognized in CVT-10216 treated-mouse tumor tissues in vivo. The repression of ALDH2 led to ACE accumulation, inducing cell apoptosis and DNA damage by the JNK/p38 MAPK signaling pathway activation in CRC.

The therapeutic potential and application of marine alkaloids in treating breast cancer

Breast cancer is a major threat to women’s health worldwide. Although the 5-year survival rate is relatively high, treating recurrent and metastatic breast cancer remains challenging. Existing anticancer drugs are often accompanied by adverse reactions; thus, there is an urgent need to explore safer and more effective treatment options. Marine natural compounds, especially alkaloids, are considered to be a potential treasure trove of new anticancer drugs due to their unique chemical structure and wide range of biological activities. A variety of marine alkaloids against breast cancer, including ecteinascidins, halichondrins, manzamines, and trabectedins, have opened new avenues for breast cancer treatment by employing multiple mechanisms, such as inducing cell apoptosis and autophagy, blocking cell cycle, inhibiting angiogenesis, targeting oncogene pathways, and inhibiting metastasis and invasion. Currently, Yondelis (trabectedin) has completed phase II clinical trials in patients with breast cancer and has shown certain efficacy. However, the clinical application of marine alkaloids still needs further research and development. This article deeply explores the mechanism of action of marine alkaloids against breast cancer and anticipates their clinical application prospects. With the deepening of research and the advancement of development, marine alkaloids are expected to bring new breakthroughs in breast cancer treatment.

Envafolimab Inhibits the Growth of Gastric Cancer Cells with Low PD-L1 Expression through the DDX20/NF-κB/TNF-α Signaling Pathway.

The mechanism of action of envafolimab (also known as KN035), a programmed death ligand 1 (PD-L1) inhibitor, in gastric adenocarcinoma patients with low PD-L1 expression is not well understood. This study aimed to observe the efficacy of envafolimab in gastric adenocarcinoma with low PD-L1 expression and explore the underlying mechanisms. The objective of this study was to explore the underlying mechanism of envafolimab in gastric cancer with low PD-L1 expression. Cytotoxicity and proliferation were evaluated by a CCK8 assay. Transwell assays were used to detect the migration and invasion ability of gastric cancer cells. The effect of envafolimab on the apoptosis of gastric cancer cells was detected by flow cytometry. The effect of envafolimab on gastric cancer cells with low PD-L1 expression was investigated via proteomics and bioinformatics analysis. A total of 19 patients with advanced gastric adenocarcinoma who received envafolimab monotherapy or combination therapy were reviewed. Among them, 4 patients had low PD-L1 expression, the objective response rate (ORR) was 75% (3/4), and the disease control rate (DCR) was 100% (4/4). In vitro experiments showed that envafolimab inhibited the proliferation, invasion, and migration of gastric cancer cells with low expression of PD-L1 and induced cell apoptosis. DDX20 may be the target of envafolimab in gastric cancer cells, and it is related to the NF-κB signaling pathway. Western blot results showed that the protein expressions of DDX20, NF-κB p65, and TNF-α in gastric cancer cells were decreased after adding envafolimab. Furthermore, the DDX20 gene was silenced by small interfering RNA to further study the effect of DDX20 on PDL1 low expression in gastric cancer cells. This study confirmed that envafolimab could inhibit the growth of gastric cancer cells with low PD-L1 expression by down-regulating DDX20 expression and regulating the NFκB/TNF-α signaling pathway.

Total triterpenoids from apple peels exert pronounced anti-breast-cancer activity in vivo and in vitro.

Apples are among the most nutritionally valuable fruits and have a history of use in traditional Chinese medicine. Triterpenoids, the primary bioactive compounds found in apples, demonstrate significant antitumor activity. Following enrichment and optimization, the total content of major triterpenoids in total triterpenoids from apple peels (ATT) reached 5.76 g kg-1. The growth of MDA-MB-231 xenograft tumors was significantly inhibited after treatment with ATT. Network pharmacology analysis conclusively identified a close association between the antitumor effect of ATT and the phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) signaling pathway. Experimental validation using MDA-MB-231 cells and a xenograft nude mouse model confirmed that ATT suppressed tumor cell proliferation effectively by modulating the PI3K-Akt signaling pathway, which was consistent with the findings from network pharmacology. The total triterpenoids from apple peels also induced cell apoptosis by mediating the PI3K-Akt signaling pathway. The total triterpenoids from apple peels can inhibit tumor cell proliferation and induce cell apoptosis effectively through the PI3K-Akt signaling pathway, suggesting that ATT holds promise as a prospective therapeutic agent for breast cancer treatment. © 2024 Society of Chemical Industry.

Alarming and calming: Dual functions of S100A9 on Mycoplasma gallisepticun infection in avian cells

Mycoplasma gallisepticum (MG) is the primary causative agent of chronic respiratory disease (CRD) in chickens, characterized by respiratory inflammation. S100A9 plays a pivotal role in modulating the inflammatory response to microbial pathogens. Our prior investigation revealed a significant upregulation of S100A9 in the lungs of chickens following MG infection. This study delves into the immunomodulatory effects of S100A9 during MG infection, demonstrating a notable increase in S100A9 levels in the lungs, immune organs, alveolar epithelial type II cells (AECII), and macrophage HD11 cells of MG-infected chicks and embryos. In MG-infected AECII cells, S100A9 overexpression significantly enhanced MG proliferation and adhesion, suppressed AVBD1, NFκB, pro-inflammatory factors (IL1β and TNFα), and chemokines, reduced apoptosis, and promoted cell proliferation, thereby facilitating MG infection. Conversely, inhibiting S100A9 produced opposing effects. In MG-infected HD11 cells, S100A9 impeded MG proliferation and adhesion, increased AVBD1, NFκB, pro-inflammatory factors, and chemokines, and induced cell apoptosis while inhibiting proliferation. Additional results demonstrated that S100A9 facilitates MG infection by modulating the TLR7/NFκB/JAK/STAT pathway in AECII/HD11 cells. In summary, S100A9 exhibits a dual role in activating/inhibiting the natural immune response through TLR7/NFκB/JAK/STAT pathway regulation. This dual role promotes MG infection in AECII cells while enabling MG to evade immune surveillance by HD11 cells, ultimately enhancing the overall infection process. These findings advance our understanding of host-pathogen interactions during MG infection and underscore S100A9's potential as a therapeutic target for CRD in chickens.

Discovery of a Highly Potent Lysine Methyltransferases G9a/NSD2 Dual Inhibitor to Treat Solid Tumors.

Both G9a and NSD2 have been recognized as promising therapeutic targets for cancer treatment. However, G9a inhibitors only showed moderate inhibitory activity against solid tumors and NSD2 inhibitors were limited to the treatment of hematological malignancies. Inspired by the advantages of dual-target inhibitors that show great potential in enhancing efficiency, we developed a series of highly potent G9a/NSD2 dual inhibitors to treat solid tumors. The candidate 16 demonstrated much enhanced antiproliferative activity compared to the selective G9a inhibitor 3 and NSD2 inhibitor 15. In addition, it exhibited superior potency in inhibiting colony formation, inducing cell apoptosis, and blocking cancer cell metastasis. Furthermore, it effectively inhibited the catalytic functions of both G9a and NSD2 in cells and exhibited significant antitumor efficacy in the PANC-1 xenograft model with good safety. Therefore, compound 16 as a highly potent G9a/NSD2 dual inhibitor presents an attractive anticancer drug candidate for the treatment of solid tumors.

MicroRNA-143 overexpression enhances the chemosensitivity of A172 glioblastoma cells to carmustine.

As an aggressive malignancy, glioblastoma multiforme (GBM) is the most common type of brain tumor. The existing treatments have shown limited achievement in increasing the overall survival of patients. Therefore, identifying the key molecules involved in GBM will provide new potential therapeutic targets. Carmustine is an alkylating agent used as a supplementary therapeutic option for GBM. However, the extensive use of carmustine has been limited by uncertainty about its efficacy. MicroRNAs (miRNAs) are essential in post-transcriptional gene regulation. Many aberrantly expressed miRNAs have been detected in various types of human cancer, including GBM. In this study, we evaluated the potential therapeutic effect of miR-143 in combination with carmustine on GBM cells. A172 cells were transfected with miR-143 mimics and then treated with carmustine. To assess the cell viability, apoptosis induction, and cell cycle progression, the MTT assay, Annexin V/PI apoptosis assay, and flow cytometry were used, respectively. Furthermore, qRT-PCR assay was applied to evaluate the expression level of genes related to apoptosis. The obtained results evidenced that miR-143 transfection could promote the sensitivity of A172 cells to carmustine and enhance carmustine-induced apoptosis via modulating the expression levels of Caspase-3, Caspase-9, Bax, and Bcl-2. Also, our results revealed that combination therapy could effectively diminish cell cycle progression in A172 cells. In conclusion, these results confirmed that miR-143 could enhance carmustine-mediated suppression of cell proliferation and improve the chemosensitivity of A172 cells to this chemotherapeutic agent. Therefore, miR-143 combination therapy may be a promising GBM treatment approach.

Retracted] Progesterone induces cell apoptosis via the CACNA2D3/Ca2+/p38 MAPK pathway in endometrial cancer.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the immunohistochemical data shown in Fig. 5C were strikingly similar to data appearing in different form in another article written by different authors at different research institutes that had already been submitted for publication elsewhere prior to the submission of this paper to Oncology Reports [Wu X, Cai D, Zhang F, Li M and Wan Q: Long noncoding RNA TUSC7 inhibits cell proliferation, migration and invasion by regulating SOCS4 (SOCS5) expression through targeting miR‑616 in endometrial carcinoma. Life Sci 231: 116549, 2019]. In addition, the CACNA203 western blot data shown in Fig. 2A‑c and B‑C respectively looked strikingly similar, even though different experiments were intended to have been shown in these figure parts. In view of the fact that the contentious data had already apparently been submitted for publication prior to the receipt of this paper at Oncology Reports, and owing to a overall lack of confidence in the presentation of the data, the Editor of has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 43: 121‑132, 2020; DOI: 10.3892/or.2019.7396].

Development of Degraders of Cyclin-Dependent Kinases 4 and 6 Based on Rational Drug Design.

Degradation of target proteins has been considered to be a promising therapeutic approach, but the rational design of compounds for degradation remains a challenge. In this study, we reasonably designed and synthesized only 10 compounds to discover effective CDK4/6 protein degraders. Among the newly synthesized compounds, 7f achieved dual degradation of CDK4/6 protein, with DC50 values of 10.5 and 2.5 nM, respectively. Compound 7f also exhibited inhibitory proliferative activity against Jurkat cells with an IC50 value of 0.18 μM. Furthermore, 7f induced cell apoptosis and G1 phase cell cycle arrest in a dose-dependent manner in Jurkat cells. In conclusion, these findings demonstrate the potential of 7f as a CDK4/6 degrader and a potential therapeutic strategy against cancer, thereby expanding the potential of CDK4/6 dual PROTACs.

Retraction: Cell detachment and apoptosis induction of immortalized human prostate epithelial cells are associated with early accumulation of a 45 kDa nuclear isoform of clusterin.

Retraction: Cell detachment and apoptosis induction of immortalized human prostate epithelial cells are associated with early accumulation of a 45 kDa nuclear isoform of clusterin.

SIGLEC15, negatively correlated with PD-L1 in HCC, could induce CD8+ T cell apoptosis to promote immune evasion

ABSTRACT Functional roles of SIGLEC15 in hepatocellular carcinoma (HCC) were not clear, which was recently found to be an immune inhibitor with similar structure of inhibitory B7 family members. SIGLEC15 expression in HCC was explored in public databases and further examined by PCR analysis. SIGLEC15 and PD-L1 expression patterns were examined in HCC samples through immunohistochemistry. SIGLEC15 expression was knocked-down or over-expressed in HCC cell lines, and CCK8 tests were used to examine cell proliferative ability in vitro. Influences of SIGLEC15 expression on tumor growth were examined in immune deficient and immunocompetent mice respectively. Co-culture system of HCC cell lines and Jurkat cells, flow cytometry analysis of tumor infiltrated immune cells and further sequencing analyses were performed to investigate how SIGLEC15 could affect T cells in vitro and in vivo. We found SIGLEC15 was increased in HCC tumor tissues and was negatively correlated with PD-L1 in HCC samples. In vitro and in vivo models demonstrated inhibition of SIGLEC15 did not directly influence tumor proliferation. However, SIGLEC15 could promoted HCC immune evasion in immune competent mouse models. Knock-out of Siglec15 could inhibit tumor growth and reinvigorate CD8+ T cell cytotoxicity. Anti-SIGLEC15 treatment could effectively inhibit tumor growth in mouse models with or without mononuclear phagocyte deletion. Bulk and single-cell RNA sequencing data of treated mouse tumors demonstrated SIGLEC15 could interfere CD8+ T cell viability and induce cell apoptosis. In all, SIGLEC15 was negatively correlated with PD-L1 in HCC and mainly promote HCC immune evasion through inhibition of CD8+ T cell viability and cytotoxicity.